History

Fact Explanation
Headache [1] [2] [3] Stretching of the diaphragma sellae the bony compartment, which contains the pituitary causes headache and it's commonly seen. [1] [2] [3]
Visual disturbance [1] [2] [3] Common complaints are due to loss of peripheral vision (eg, bumping into walls), or visual loss in one eye. This is due to either compression or invasion of the optic nerve and it's pathway by the pituitary mass.The symptoms and signs vary depending on where the pathway of the optic nerve is compressed. Prechiasmatic compression results in symptoms affecting one eye, while chiasmatic lesions result in quadrantanopsia or bitemporal hemianopia. Homonymous hemianopia can result from post-chiasmatic lesions . [1] [2] [3]
poor growth in a child [1] [2] [3] [6] [7] This is due to hypopituitarism which occurs either due to disruption of the hypothalamic-pituitary portal system or the normal pituitary tissue by the tumour. Growth hormone deficiency gives rise to poor growth. [1] [2] [3] [6] [7]
Cold intolerance, constipation, slowing of mentation, dry skin and coarse hair, and change in the shape of the face [1] [2] [3] [6] [7] This is due to hypothyroidism due to thyroid stimulating hormone deficiency in turn causing deficiency of thyroxin. [1] [2] [3] [6] [7]
Pubertal delay in girls [1] [2] [3] [9] Breast development (thelarche) is delayed in adolescent girls while a reduction in breast size or a softening of breasts are seen in post pubertal women. This is due to hypoestrogenism.[1] [2] [3] [9]
Pubertal delay in boys [1] [2] [3] [9] Scrotal development and testicular enlargement is delayed in adolescent boys. [1] [2] [3] [9]
Galactorrhoea [1] [2] [3] [9] May results from Hyperprolactinemia owing to the interruption of hypothalamic-pituitary portal axis. [1] [2] [3] [9]
Polyuria, Nocturia and polydipsia. [1] [2] [3] [8] This is due to diabetes insipidus due to inadequate secretion of ADH from posterior pitiutary. Presence of nocturia or diluted urine in the morning first void is also suggestive of diabetes insipidus. [1] [2] [3] [8]
Hyper pigmentation [1] [2] [3] [10] This is often noticed by the patient when there's increased pigmentation of the scars, gingivae, and palmer creases. This is due to increased Adrenocorticotrophin secretion by the pituitary due to loss of negative feed back from corticosteroids which are usually secreted from the adrenal glands. [1] [2] [3] [10]
Previous history of excessive weight gain with truncal obesity, easy bruising, stretch marks on the breasts, arms, abdomen, and thighs [4] [5] These features are suggestive of previous Cushing's syndrome due to adrenal adenoma. These features are due to excessive corticosteroid secretion. [4] [5]
References
  1. ANDERSON J R, ANTOUN N, BURNET N, CHATTERJEE K, EDWARDS O, PICKARD J D, SARKIES N. Neurology of the pituitary gland. Journal of Neurology, Neurosurgery & Psychiatry [online] 1999 June, 66(6):703-721 [viewed 01 September 2014] Available from: doi:10.1136/jnnp.66.6.703
  2. YOUNG LW, LIM GH, FORBES GB, BRYSON MF. Postadrenalectomy pituitary adenoma (Nelson's syndrome) in childhood: clinical and roentgenologic detection. American Journal of Roentgenology [online] 1976 March, 126(3):550-559 [viewed 01 September 2014] Available from: doi:10.2214/ajr.126.3.550
  3. BARBER T. M., ADAMS E., ANSORGE O., BYRNE J. V., KARAVITAKI N., WASS J. A. H.. Nelson's syndrome. European Journal of Endocrinology [online] December, 163(4):495-507 [viewed 01 September 2014] Available from: doi:10.1530/EJE-10-0466
  4. CASTINETTI FREDERIC, MORANGE ISABELLE, CONTE-DEVOLX BERNARD, BRUE THIERRY. Cushing’s disease. Array [online] 2012 December [viewed 01 September 2014] Available from: doi:10.1186/1750-1172-7-41
  5. ZADA GABRIEL. Diagnosis and Multimodality Management of Cushing’s Disease: A Practical Review. International Journal of Endocrinology [online] 2013 December, 2013:1-7 [viewed 01 September 2014] Available from: doi:10.1155/2013/893781
  6. MUNIR ALIA, NEWELL-PRICE JOHN. Nelson's Syndrome. Arq Bras Endocrinol Metab [online] 2007 November, 51(8):1392-1396 [viewed 01 September 2014] Available from: doi:10.1590/S0004-27302007000800026
  7. POZZA CARLOTTA, GRAZIADIO CHIARA, GIANNETTA ELISA, LENZI ANDREA, ISIDORI ANDREA M.. Management Strategies for Aggressive Cushing's Syndrome: From Macroadenomas to Ectopics. Journal of Oncology [online] 2012 December, 2012:1-9 [viewed 01 September 2014] Available from: doi:10.1155/2012/685213
  8. MAKARYUS A. N, MCFARLANE S. I. Diabetes insipidus: diagnosis and treatment of a complex disease.. Cleveland Clinic Journal of Medicine [online] 2006 January, 73(1):65-71 [viewed 01 September 2014] Available from: doi:10.3949/ccjm.73.1.65
  9. BRANDLE M.. Galactorrhoea and pituitary mass: a typical prolactinoma?. [online] 2000 April, 76(894):232-234 [viewed 01 September 2014] Available from: doi:10.1136/pmj.76.894.232
  10. DALVI ABHAYN, THAPAR PINKYM, VIJAY KUMAR K, KAMBLE RANJEETS, REGE SAMEERA, DESHPANDE APARNAA, SHAH NALINIS, MENON PADMAS. Laparoscopic adrenalectomy: Gaining experience by graded approach. J Min Access Surg [online] 2006 December [viewed 01 September 2014] Available from: doi:10.4103/0972-9941.26649

Examination

Fact Explanation
Reduced height and poor growth [1] [2] [3] [4] [7] Pituitary lesions can give rise to growth hormone deficiency and reduction in the height and growth velocity. Previous Cushing's syndrome may have caused weight gain but it's important to measure the weight as well. [1] [2] [3] [4] [7]
Bradycardia or Tachycardia [1] [2] [3] [4] [7] If there's hypothyroidism due to Thyroxine deficiency, bradycardia occurs but in acute adrenal insufficiency, a reflex tachycardia may be present. [1] [2] [3] [4] [7]
Hypertension or postural hypotension [1] [2] [3] [4] [7] Hypertension can occur due to two reasons either due to hypercortisolism of Previous Cushing's syndrome or as a pitfall in the management where there's excessive mineralocorticoid replacement. Hypotension is also present in some. Especially a postural drop is noted in patients with acute adrenal crisis or again as a pitfall in the management where there's inadequacy in the mineralocortcoid replacement. [1] [2] [3] [4] [7]
Hyperpigmentation of the skin [1] [2] [3] [4] [7] This is due to increased adrenocorticotrophin (ACTH) by the pitiutary due to loss of negative feed back from adrenal corticosterids. Patients usually appear hyperpigmented in linea nigra, scars, gingivae, palmer creases, scrotum and areolae. [1] [2] [3] [4] [7]
Assessment of the pubertal stage [1] [2] [3] [4] [6] Excessive adrenal androgens in patients with previous Cushing syndrome can cause premature pubarche. In post pubertal females, secondary hypoestrogenism results in softening and reduction in the size of breasts where as breast development is delayed in adolescent girls. In males, loss of body hair, small soft testes, increased upper–to–lower segment ratio are some features seen. [1] [2] [3] [4] [6]
Visual disturbances- Decreased visual acuity, visual field defects, papilloedema or optic atrophy [1] [2] [3] [8] Visual acuity, visual field assessment by confrontation, and ophthalmological examination for papilledema or optic nerve atrophy should be done. Visual defects are due to invasion or compression of optic nerve and it's pathway by the tumour. Prechiasmatic compression affects one eye, while chiasmatic lesions result in quadrantanopsia or bitemporal hemianopia. Homonymous hemianopia can result from post-chiasmatic lesions [1] [2] [3] [8]
Reduced sensation of the forehead [1] [2] [3] [8] If there's tumor invasion of the ipsilateral cavernous sinus, first division of trigeminal nerve may be involved causing reduced sensation of the forehead [1] [2] [3] [8]
Ocular movement defects [1] [2] [3] [8] [9] If the tumour invades the ipsilateral cavernous sinus, III, IV, VI cranial nerves may be involved causing extra-ocular muscle paralysis and movement defects [1] [2] [3 [8] [9]
Hyporeflexia and delayed relaxation [1] [2] [3] This can be present in patients with hypothyroidism which resulted from reduced thyroxine secretion. [1] [2] [3]
References
  1. ANDERSON J R, ANTOUN N, BURNET N, CHATTERJEE K, EDWARDS O, PICKARD J D, SARKIES N. Neurology of the pituitary gland. Journal of Neurology, Neurosurgery & Psychiatry [online] 1999 June, 66(6):703-721 [viewed 01 September 2014] Available from: doi:10.1136/jnnp.66.6.703
  2. YOUNG LW, LIM GH, FORBES GB, BRYSON MF. Postadrenalectomy pituitary adenoma (Nelson's syndrome) in childhood: clinical and roentgenologic detection. American Journal of Roentgenology [online] 1976 March, 126(3):550-559 [viewed 01 September 2014] Available from: doi:10.2214/ajr.126.3.550
  3. BARBER T. M., ADAMS E., ANSORGE O., BYRNE J. V., KARAVITAKI N., WASS J. A. H.. Nelson's syndrome. European Journal of Endocrinology [online] December, 163(4):495-507 [viewed 01 September 2014] Available from: doi:10.1530/EJE-10-0466
  4. MUNIR ALIA, NEWELL-PRICE JOHN. Nelson's Syndrome. Arq Bras Endocrinol Metab [online] 2007 November, 51(8):1392-1396 [viewed 01 September 2014] Available from: doi:10.1590/S0004-27302007000800026
  5. POZZA CARLOTTA, GRAZIADIO CHIARA, GIANNETTA ELISA, LENZI ANDREA, ISIDORI ANDREA M.. Management Strategies for Aggressive Cushing's Syndrome: From Macroadenomas to Ectopics. Journal of Oncology [online] 2012 December, 2012:1-9 [viewed 01 September 2014] Available from: doi:10.1155/2012/685213
  6. BRANDLE M.. Galactorrhoea and pituitary mass: a typical prolactinoma?. [online] 2000 April, 76(894):232-234 [viewed 01 September 2014] Available from: doi:10.1136/pmj.76.894.232
  7. DALVI ABHAYN, THAPAR PINKYM, VIJAY KUMAR K, KAMBLE RANJEETS, REGE SAMEERA, DESHPANDE APARNAA, SHAH NALINIS, MENON PADMAS. Laparoscopic adrenalectomy: Gaining experience by graded approach. J Min Access Surg [online] 2006 December [viewed 01 September 2014] Available from: doi:10.4103/0972-9941.26649
  8. ARSHAD FAHEEM, LAWAY BASHIR AHMAD, BHAT MANZOOR AHMAD, IRFAN SHOWKAT HAKIM, KOTWAL SUMAN, AHMAD MIR SHAHNAZ. Leksell Gamma Knife : An Effective Non Invasive Treatment for Rare Case of Nelson’s Syndrome. Int J Endocrinol Metab [online] 2013 July [viewed 01 September 2014] Available from: doi:10.5812/ijem.10225
  9. GARG MK, BRAR KS, BHARWAJ REENA, PATHAK HC, GILL MANEET, GUNDGURTHI ABHAY, KHARB SANDEEP. Nelson′s syndrome presenting as bilateral oculomotor palsy. Indian J Endocr Metab [online] 2013 December [viewed 01 September 2014] Available from: doi:10.4103/2230-8210.122643

Differential Diagnoses

Fact Explanation
Hypopituitarism [2] [3] Hypopituitarism is an insufficiency of pituitary hormone secretion that occurs from pituitary or hypothalamic disease. The onset can be at any time of life with pituitary enzyme deficiencies. They present with mainly poor growth, hypothyroidism and pubertal delay [2] [3]
Adrenal Hypoplasia [4] Adrenocorticotropic hormone (ACTH) deficiency and defects of the ACTH hormone receptor cause hypoplasia of the adrenal cortex. Patients often present in acute adrenal crisis with dehydration, hyponatremia, hyperkalemia, hypotension, or hypoglycemia. [4]
Adrenal Insufficiency (Addison disease) [5] [6] This can be primary, which occurs when there's problem in the adrenal gland itself, or secondary which occurs when a lack of secretion of corticotropin-releasing hormone (CRH) from the hypothalamus or of adrenocorticotropic hormone (ACTH) from the pituitary leads to hypofunction of the adrenal cortex. They often present with hypoglycemia, orthostatic hypotension. This could be autoimmune in nature, therefore when a child presents with hyper pigmentation this should be considered as a main differential diagnosis and should look for evidence of other autoimmune diseases. [5] [6]
Congenital Adrenal Hyperplasia [1] Congeital adrenal hyperplasia (CAH) is an autosomal recessive disorder group where each consists an enzyme deficiency involved in the synthesis of either cortisol or aldosterone, or both. Deficiency of 21-hydroxylase is the most common form of CAH. [1]
Craniopharyngioma [7] [8] Craniopharyngioma is a benign, slow-growing tumor that grows in the sella and suprasellar space and considered as a differential diagnosis [7] [8]
Hemachromatosis [9] [10] Hemochromatosis is the most common autosomal recessive genetic disorder owing to the abnormal iron accumilations in parenchymal organs, resulting in organ toxicity. Hereditary hemochromatosis patients may be asymptomatic or present with general and organ-related features.Skin pigmentation with bronze color is common. They usually end up in liver disease, therefore jaundice is seen. [9] [10]
References
  1. LOECHNER KAREN J., MCLAUGHLIN JAMES T., CALIKOGLU ALI S.. Alternative Strategies for the Treatment of Classical Congenital Adrenal Hyperplasia: Pitfalls and Promises. International Journal of Pediatric Endocrinology [online] 2010 December, 2010:1-10 [viewed 01 September 2014] Available from: doi:10.1155/2010/670960
  2. GARG MK, BRAR KS, SURYANARAYANA KM. Adult hypopituitarism: Are we missing or is it clinical lethargy?. Indian J Endocr Metab [online] 2011 December [viewed 01 September 2014] Available from: doi:10.4103/2230-8210.83400
  3. FADOUKHAIR ZOUHOUR, AMZERIN MOUNIA, ISMAILI NABIL, BELBARAKA RHIZLANE, LATIB RACHIDA, SBITTI YASSIR, M'RABTI HIND, BOUTAYEB SABER, ICHOU MOHAMMED, ERRIHANI HASSAN. Symptomatic hypopituitarism revealing primary suprasellar lymphoma. Array [online] 2010 December [viewed 01 September 2014] Available from: doi:10.1186/1472-6823-10-19
  4. METWALLEY KOTB, FARGHALY HEKMA. X-linked congenital adrenal hypoplasia associated with hypospadias in an Egyptian baby: a case report. Array [online] 2012 December [viewed 01 September 2014] Available from: doi:10.1186/1752-1947-6-428
  5. ROSS IAN LOUIS, LEVITT NAOMI S., DASTGIRI SAEED. Addison’s Disease Symptoms – A Cross Sectional Study in Urban South Africa. PLoS ONE [online] 2013 January [viewed 01 September 2014] Available from: doi:10.1371/journal.pone.0053526
  6. LEELARATHNA L., POWRIE J.K., CARROLL P.V.. Thomas Addison's disease after 154 years: modern diagnostic perspectives on an old condition. QJM [online] December, 102(8):569-573 [viewed 01 September 2014] Available from: doi:10.1093/qjmed/hcp053
  7. GARNETT MATTHEW R, PUGET STéPHANIE, GRILL JACQUES, SAINTE-ROSE CHRISTIAN. Craniopharyngioma. Orphanet J Rare Dis [online] 2007 December [viewed 01 September 2014] Available from: doi:10.1186/1750-1172-2-18
  8. TRIVIN CHRISTINE, BUSIAH KANETEE, MAHLAOUI NIZAR, RECASENS CHRISTOPHE, SOUBERBIELLE JEAN-CLAUDE, ZERAH MICHEL, SAINTE-ROSE CHRISTIAN, BRAUNER RAJA. Childhood craniopharyngioma: greater hypothalamic involvement before surgery is associated with higher homeostasis model insulin resistance index. Array [online] 2009 December [viewed 01 September 2014] Available from: doi:10.1186/1471-2431-9-24
  9. LIMDI J.K., CRAMPTON J.R.. Hereditary haemochromatosis. QJM [online] December, 97(6):315-324 [viewed 01 September 2014] Available from: doi:10.1093/qjmed/hch065
  10. MCCARTHY G. M, CROWE J., MCCARTHY C. J, EUSTACE S., KENNY D.. Hereditary hemochromatosis: a common, often unrecognized, genetic disease.. Cleveland Clinic Journal of Medicine [online] 2002 March, 69(3):224-226 [viewed 01 September 2014] Available from: doi:10.3949/ccjm.69.3.224

Investigations - for Diagnosis

Fact Explanation
Serum Adrenocorticotropin (ACTH) level [1] [2] [3] [4][5] In Nelson syndrome the level of ACTH is very high and other derivatives of the precursor peptide, proopiomelanocortin (POMC). [1] [2] [3] [4] [5]
Thyroid function test [5] [6] Free thyroxine (T4) levels can be below the lower limit of the reference range even though clinical hypothyroidism may not be apparent.Thyroid-stimulating hormone (TSH) levels can either be low, normal, or slightly elevated. [5] [6]
Serum Prolactin level [4] [5] [6] Dopaminergic inhibition due to invasion of the pituitary stalk or hypothalamic-pituitary portal system results in hyperprolactinemia. Patients with pituitary macroadenomas tend to have very high Prolactin levels. [4] [5] [6]
Serum Growth hormone level [4] [5] [6] Since there's inadequate secretion of growth hormone by the anterior pituitary, the serum level may be low [4] [5] [6]
Serum Gonadotropin level [4] [5] [6] Hyperprolactinemia causes hypogonadotropic hypogonadism therefore gonadotrophin levels are low. [4] [5] [6]
Urine osmolality or specific gravity test [5] [6] [7] If the tumor has destroyed the posterior part of the pituitary gland, central diabetes insipidus occurs. In normal people, the urine osmolality or specific gravity should be greater than 600-700 mOsm/kg or 1.010 respectively in an early morning urine specimen. But in these patients urine is dilute. [5] [6] [7]
MRI scan of the pituitary and parasellar region [1] [3] This can demonstrate the tumor if it's large and shows compression or invasion of surrounding structures as well therefore helps in the management. [1] [3]
Visual field assessment by perimetry [1] [3] To assess the visual field as visual field defects are common due to compression or invasion of the optic nerve and it's pathway. [1] [3]
Biopsy of the tumour [3] Tumors are immunostain positive for ACTH and tumors have cytological features as in any malignancy such as increased cellular proliferation, with mitoses and cellular and nuclear pleomorphism. [3]
References
  1. ZADA GABRIEL. Diagnosis and Multimodality Management of Cushing’s Disease: A Practical Review. International Journal of Endocrinology [online] 2013 December, 2013:1-7 [viewed 01 September 2014] Available from: doi:10.1155/2013/893781
  2. MUNIR ALIA, NEWELL-PRICE JOHN. Nelson's Syndrome. Arq Bras Endocrinol Metab [online] 2007 November, 51(8):1392-1396 [viewed 01 September 2014] Available from: doi:10.1590/S0004-27302007000800026
  3. BARBER T. M., ADAMS E., ANSORGE O., BYRNE J. V., KARAVITAKI N., WASS J. A. H.. Nelson's syndrome. European Journal of Endocrinology [online] December, 163(4):495-507 [viewed 01 September 2014] Available from: doi:10.1530/EJE-10-0466
  4. ARSHAD FAHEEM, LAWAY BASHIR AHMAD, BHAT MANZOOR AHMAD, IRFAN SHOWKAT HAKIM, KOTWAL SUMAN, AHMAD MIR SHAHNAZ. Leksell Gamma Knife : An Effective Non Invasive Treatment for Rare Case of Nelson’s Syndrome. Int J Endocrinol Metab [online] 2013 July [viewed 01 September 2014] Available from: doi:10.5812/ijem.10225
  5. ANDERSON J R, ANTOUN N, BURNET N, CHATTERJEE K, EDWARDS O, PICKARD J D, SARKIES N. Neurology of the pituitary gland. Journal of Neurology, Neurosurgery & Psychiatry [online] 1999 June, 66(6):703-721 [viewed 01 September 2014] Available from: doi:10.1136/jnnp.66.6.703
  6. POZZA CARLOTTA, GRAZIADIO CHIARA, GIANNETTA ELISA, LENZI ANDREA, ISIDORI ANDREA M.. Management Strategies for Aggressive Cushing's Syndrome: From Macroadenomas to Ectopics. Journal of Oncology [online] 2012 December, 2012:1-9 [viewed 01 September 2014] Available from: doi:10.1155/2012/685213
  7. SMITH M.. Pituitary disease and anaesthesia. [online] 2000 July, 85(1):3-14 [viewed 01 September 2014] Available from: doi:10.1093/bja/85.1.3

Investigations - Fitness for Management

Fact Explanation
Full blood count [1] [2] To exclude anemia prior to surgery [1] [2]
Coagulation studies [1] [2] To exclude any coagulopathy prior to surgery [1] [2]
Renal function tests- Serum Creatinine, Blood urea nitrogen [1] [2] To exclude any renal dysfunction and assess the fitness for anesthesia [1] [2]
Electrocardiogram [3] [4] These patients are likely to have suffered from Cushing's syndrome therefore ECG abnormalities such as high voltage QRS complexes and inverted T waves, Left ventricular hypertrophy and asymmetric septal hypertrophy are observed frequently in patients with Cushing’s syndrome. [3] [4]
Fasting blood sugar [3] [4] [5] In Cushing's syndrome, glucose intolerance or frank diabetes occurs in 60% of patients and is related to reduced insulin secretion and non‐insulin‐mediated glucose disposal in the presence of elevated insulin concentrations. [3] [4] [5]
Serum cholesterol [3] [4] [6] These patients are likely to have suffered from Cushing's syndrome and they usually have abnormal lipid levels. In addition to that untreated hypothyroidism can also give rise to high cholesterol levels. [3] [4] [6]
References
  1. KUMAR A, SRIVASTAVA U. Role of routine laboratory investigations in preoperative evaluation J Anaesthesiol Clin Pharmacol [online] 2011, 27(2):174-179 [viewed 1 September 2014] Available from: doi:10.4103/0970-9185.81824
  2. SHULMAN M. A., THOMPSON B. R.. I. Not fit for a haircut ... how should we assess fitness and stratify risk for surgery?. British Journal of Anaesthesia [online] December, 112(6):955-957 [viewed 1 September 2014] Available from: doi:10.1093/bja/aeu003 2014] Available from: doi:10.1093/bja/aeu003
  3. RESMINI EUGENIA. Persistent Comorbidities in Cushing’s Syndrome after Endocrine Cure. Advances in Endocrinology [online] 2014 December, 2014:1-14 [viewed 01 September 2014] Available from: doi:10.1155/2014/231432
  4. SMITH M.. Pituitary disease and anaesthesia. [online] 2000 July, 85(1):3-14 [viewed 01 September 2014] Available from: doi:10.1093/bja/85.1.3
  5. LANSANG M. C., HUSTAK L. K.. Glucocorticoid-induced diabetes and adrenal suppression: How to detect and manage them. Cleveland Clinic Journal of Medicine [online] December, 78(11):748-756 [viewed 01 September 2014] Available from: doi:10.3949/ccjm.78a.10180
  6. LAUKKARINEN JOHANNA, SAND JUHANI, NORDBACK ISTO. The Underlying Mechanisms: How Hypothyroidism Affects the Formation of Common Bile Duct Stones—A Review. HPB Surgery [online] 2012 December, 2012:1-7 [viewed 01 September 2014] Available from: doi:10.1155/2012/102825

Investigations - Followup

Fact Explanation
Growth monitoring [2] Growth parameters are need to be monitored especially giving attention to height as these patients are likely to be stunted due to growth hormone deficiency, as well as due to hypothyroidism. Growth velocity can be measured when serial height, weight values are present. This also helps in adjusting the growth hormone therapy in the management. [2]
Blood pressure monitoring [1] [7] [8] These patients are put on mineralocorticoids and glucorcoticoids as a part of the management. Both of these hormones when excessive cause water retention contributing to high blood pressure. Also adrenal rest tissue in the testis can get stimulated with Nelson syndrome and cause recurrence of Cushing's syndrome. Therefore monitoring of blood pressure in the follow up is necessary [1] [7] [8]
Overnight growth hormone sampling [1] [2] [3] As these patients are having growth hormone deficiency, this test is done to monitor their growth hormone level. [1] [2] [3]
Thyroid function tests [1] [2] [3] This should be measured at least every 6 months as they are likely to be hypothyroid and hypopituitarism can also occur as a complication. [1] [2] [3]
Serum sodium [4] [5] Children on treatment with Desmopressin need to have regular sodium measurements as this drug may interfere with serum sodium level. [4] [5]
Perimetry [9] Residual tumour tissue may give rise to visual symptoms in the follow up, therefore, if the patient complains of any visual disturbances, these tests need to be done. [9]
Serum ACTH [1] [2] This is done to detect hypopituitarism which can occur as a complication of Nelson syndrome. Low ACTH level is seen in Hypopitiuitarism. [1] [2]
Seminal fluid analysis [6] There could be adrenal rest tissue in the testis, which have migrated during embryogenesis. This can be stimulated in Nelson's syndrome and known to cause painful testicular enlargement and sometimes even oligozoospermia. Therefore seminal fluid analysis in a male is important if symptoms are present. [6]
References
  1. BARBER T. M., ADAMS E., ANSORGE O., BYRNE J. V., KARAVITAKI N., WASS J. A. H.. Nelson's syndrome. European Journal of Endocrinology [online] December, 163(4):495-507 [viewed 01 September 2014] Available from: doi:10.1530/EJE-10-0466
  2. MUNIR ALIA, NEWELL-PRICE JOHN. Nelson's Syndrome. Arq Bras Endocrinol Metab [online] 2007 November, 51(8):1392-1396 [viewed 01 September 2014] Available from: doi:10.1590/S0004-27302007000800026
  3. ANDERSON J R, ANTOUN N, BURNET N, CHATTERJEE K, EDWARDS O, PICKARD J D, SARKIES N. Neurology of the pituitary gland. Journal of Neurology, Neurosurgery & Psychiatry [online] 1999 June, 66(6):703-721 [viewed 01 September 2014] Available from: doi:10.1136/jnnp.66.6.703
  4. PERIANAYAGAM A., STERNS R. H., SILVER S. M., GRIEFF M., MAYO R., HIX J., KOUIDES R.. DDAVP Is Effective in Preventing and Reversing Inadvertent Overcorrection of Hyponatremia. Clinical Journal of the American Society of Nephrology [online] 2008 February, 3(2):331-336 [viewed 01 September 2014] Available from: doi:10.2215/​CJN.03190807
  5. VAIDYA C., HO W., FREDA B. J.. Management of hyponatremia: Providing treatment and avoiding harm. Cleveland Clinic Journal of Medicine [online] December, 77(10):715-726 [viewed 01 September 2014] Available from: doi:10.3949/ccjm.77a.08051
  6. CLAAHSEN-VAN DER GRINTEN H. L, DUTHOI K., OTTEN B. J, D'ANCONA F. C H, HULSBERGEN-VD KAA C. A, HERMUS A. R M M. An adrenal rest tumour in the perirenal region in a patient with congenital adrenal hyperplasia due to congenital 3 -hydroxysteroid dehydrogenase deficiency. European Journal of Endocrinology [online] 2008 July, 159(4):489-491 [viewed 03 September 2014] Available from: doi:10.1530/EJE-08-0311
  7. CASTINETTI FREDERIC, MORANGE ISABELLE, CONTE-DEVOLX BERNARD, BRUE THIERRY. Cushing’s disease. Array [online] 2012 December [viewed 03 September 2014] Available from: doi:10.1186/1750-1172-7-41
  8. DAVIES M.. Anaesthesia and adrenocortical disease. Continuing Education in Anaesthesia, Critical Care & Pain [online] 2005 August, 5(4):122-126 [viewed 03 September 2014] Available from: doi:10.1093/bjaceaccp/mki033
  9. GARG MK, BRAR KS, BHARWAJ REENA, PATHAK HC, GILL MANEET, GUNDGURTHI ABHAY, KHARB SANDEEP. Nelson′s syndrome presenting as bilateral oculomotor palsy. Indian J Endocr Metab [online] 2013 December [viewed 01 September 2014] Available from: doi:10.4103/2230-8210.122643

Investigations - Screening/Staging

Fact Explanation
Insulinlike growth factor–1 (IGF-1) and insulinlike growth factor–binding protein-3 (IGF-BP3) level [1] [2] [3] [4] This is used as a screening method for growth hormone deficiency in children older than 3 years. [1] [2] [3] [4]
References
  1. VIK-MO E. O., OKSNES M., PEDERSEN P.-H., WENTZEL-LARSEN T., RODAHL E., THORSEN F., SCHREINER T., AANDERUD S., LUND-JOHANSEN M.. Gamma knife stereotactic radiosurgery of Nelson syndrome. European Journal of Endocrinology [online] 2008 November, 160(2):143-148 [viewed 01 September 2014] Available from: doi:10.1530/EJE-08-0687
  2. BARBER T. M., ADAMS E., ANSORGE O., BYRNE J. V., KARAVITAKI N., WASS J. A. H.. Nelson's syndrome. European Journal of Endocrinology [online] December, 163(4):495-507 [viewed 01 September 2014] Available from: doi:10.1530/EJE-10-0466
  3. ANDERSON J R, ANTOUN N, BURNET N, CHATTERJEE K, EDWARDS O, PICKARD J D, SARKIES N. Neurology of the pituitary gland. Journal of Neurology, Neurosurgery & Psychiatry [online] 1999 June, 66(6):703-721 [viewed 01 September 2014] Available from: doi:10.1136/jnnp.66.6.703
  4. MUNIR ALIA, NEWELL-PRICE JOHN. Nelson's Syndrome. Arq Bras Endocrinol Metab [online] 2007 November, 51(8):1392-1396 [viewed 01 September 2014] Available from: doi:10.1590/S0004-27302007000800026

Management - General Measures

Fact Explanation
Parental and patient education [1] [2] [3] [4] This is important especially regarding the etiology, nature, course and prognosis of the disease, available treatment options and the importance of follow up. Patient should be reassured especially regarding pubertal delay and counseling maybe needed. [1] [2] [3] [4]
Regular follow up [1] [2] [3] [4] Proper periodical follow up is needed to assess the enzyme deficiencies and the adequacy of replacement. [1] [2] [3] [4]
References
  1. BARBER T. M., ADAMS E., ANSORGE O., BYRNE J. V., KARAVITAKI N., WASS J. A. H.. Nelson's syndrome. European Journal of Endocrinology [online] December, 163(4):495-507 [viewed 01 September 2014] Available from: doi:10.1530/EJE-10-0466
  2. MUNIR ALIA, NEWELL-PRICE JOHN. Nelson's Syndrome. Arq Bras Endocrinol Metab [online] 2007 November, 51(8):1392-1396 [viewed 01 September 2014] Available from: doi:10.1590/S0004-27302007000800026
  3. ANDERSON J R, ANTOUN N, BURNET N, CHATTERJEE K, EDWARDS O, PICKARD J D, SARKIES N. Neurology of the pituitary gland. Journal of Neurology, Neurosurgery & Psychiatry [online] 1999 June, 66(6):703-721 [viewed 01 September 2014] Available from: doi:10.1136/jnnp.66.6.703
  4. GARG MK, BRAR KS, BHARWAJ REENA, PATHAK HC, GILL MANEET, GUNDGURTHI ABHAY, KHARB SANDEEP. Nelson′s syndrome presenting as bilateral oculomotor palsy. Indian J Endocr Metab [online] 2013 December [viewed 01 September 2014] Available from: doi:10.4103/2230-8210.122643

Management - Specific Treatments

Fact Explanation
Medical management with cabergoline [7] [8] This is a dopamine receptor agonist which causes decline and normalization of adrenocorticotropin (ACTH) levels and also resolution of the pituitary macroadenoma or microadenoma [7] [8]
Medical management with octreotide or other analogue of somatostatin [7] [9] [10] Helpful to control ACTH levels, although only useful until definitive treatment is undertaken as it does not cause much of tumor shrinkage. Because it also suppresses other hormones, including insulin, it may result in carbohydrate intolerance too. [7] [9] [10]
Medical management with cyproheptadine [7] [10] cyproheptadine with and without bromocriptine is shown to cause significant reduction in plasma ACTH and prolactin concentration [7] [10]
Medical management with sodium valproate. [10] This has also shown to reduce plasma ACTH level. [10]
Radiotherapy [2] [3] [4] [7] Important in patients with Nelson syndrome. But has a high risk of adverse effects. Recently stereotactic radiosurgery, called gamma knife surgery (GKS), has been performed in secretory pituitary tumors including Nelson syndrome tumors and became successful [2] [3] [4] [7]
Surgical management [4] [5] [6] [7] Treatment of choice for large tumors producing acute compression of the optic nerve, optic pathway and other surrounding vital structures. Transsphenoidal surgery is optimal because it has the lowest risk of hypothalamic injury. [4] [5] [6]
Management with Temozolomide [1] This is a type of chemotherapy used to treat primary brain tumors called glioblastoma can also be used. [1] [7]
Steroid replacement [8] [11] As these patients have undergone bilateral adrenalectomy, they need to have adrenal steroid with glucocorticoids and mineralocorticoids Inadequate mineralocorticoid replacement results in increased glucocorticoid requirement that can cause re-appearance of Cushing's syndrome. [8] [11]
References
  1. MOYES V J, ALUSI G, SABIN H I, EVANSON J, BERNEY D M, KOVACS K, MONSON J P, PLOWMAN P N, DRAKE W M. Treatment of Nelson's syndrome with temozolomide. European Journal of Endocrinology [online] December, 160(1):115-119 [viewed 01 September 2014] Available from: doi:10.1530/EJE-08-0557
  2. VIK-MO E. O., OKSNES M., PEDERSEN P.-H., WENTZEL-LARSEN T., RODAHL E., THORSEN F., SCHREINER T., AANDERUD S., LUND-JOHANSEN M.. Gamma knife stereotactic radiosurgery of Nelson syndrome. European Journal of Endocrinology [online] 2008 November, 160(2):143-148 [viewed 01 September 2014] Available from: doi:10.1530/EJE-08-0687
  3. ARSHAD FAHEEM, LAWAY BASHIR AHMAD, BHAT MANZOOR AHMAD, IRFAN SHOWKAT HAKIM, KOTWAL SUMAN, AHMAD MIR SHAHNAZ. Leksell Gamma Knife : An Effective Non Invasive Treatment for Rare Case of Nelson’s Syndrome. Int J Endocrinol Metab [online] 2013 July [viewed 01 September 2014] Available from: doi:10.5812/ijem.10225
  4. KELLY P. A., SAMANDOURAS G., GROSSMAN A. B., AFSHAR F., BESSER G. M., JENKINS P. J.. Neurosurgical Treatment of Nelson’s Syndrome. The Journal of Clinical Endocrinology & Metabolism [online] 2002 December, 87(12):5465-5469 [viewed 01 September 2014] Available from: doi:10.1210/jc.2002-020299
  5. YOUNG LW, LIM GH, FORBES GB, BRYSON MF. Postadrenalectomy pituitary adenoma (Nelson's syndrome) in childhood: clinical and roentgenologic detection. American Journal of Roentgenology [online] 1976 March, 126(3):550-559 [viewed 01 September 2014] Available from: doi:10.2214/ajr.126.3.550
  6. MASSOUD A F, POWELL M, WILLIAMS R A, HINDMARSH P C, BROOK C G D. Transsphenoidal surgery for pituitary tumours. Archives of Disease in Childhood [online] 1997 May, 76(5):398-404 [viewed 01 September 2014] Available from: doi:10.1136/adc.76.5.398
  7. MUNIR ALIA, NEWELL-PRICE JOHN. Nelson's Syndrome. Arq Bras Endocrinol Metab [online] 2007 November, 51(8):1392-1396 [viewed 01 September 2014] Available from: doi:10.1590/S0004-27302007000800026
  8. BARBER T. M., ADAMS E., ANSORGE O., BYRNE J. V., KARAVITAKI N., WASS J. A. H.. Nelson's syndrome. European Journal of Endocrinology [online] December, 163(4):495-507 [viewed 01 September 2014] Available from: doi:10.1530/EJE-10-0466
  9. DE HERDER W. W., VAN DER LELY A. J., LAMBERTS S. W.. Somatostatin analogue treatment of neuroendocrine tumours.. Postgraduate Medical Journal [online] 1996 July, 72(849):403-408 [viewed 01 September 2014] Available from: doi:10.1136/pgmj.72.849.403
  10. MERCADO-ASIS LEILANI B., YANOVSKI JACK A., TRACER HOWARD L., CHIK CONSTANCE L., CUTLER GORDON B.. Acute Effects of Bromocriptine, Cyproheptadine, and Valproic Acid on Plasma Adrenocorticotropin Secretion in Nelson’s Syndrome. The Journal of Clinical Endocrinology & Metabolism [online] 1997 February, 82(2):514-517 [viewed 01 September 2014] Available from: doi:10.1210/jcem.82.2.3742
  11. GUNDGURTHI A, KHARB S, GARG MK, BRAR KS, BHARWAJ R, PATHAK HC, GILL M. Nelson's syndrome presenting as bilateral oculomotor palsy. Indian J Endocrinol Metab [online] 2013 Nov, 17(6):1114-6 [viewed 01 September 2014] Available from: doi:10.4103/2230-8210.122643