Selected endocrinopathy BY DR. IMAFIDOR(1)

A pheochromocytoma is a catecholamine-producing neuroendocrine tumor arising from chromaffin cells of the adrenal medulla or extra‑adrenal chromaffin tissue; ~85% adrenal, ~15% extra‑adrenal.

Common features include hypertension (sustained or paroxysmal), headache, palpitations, diaphoresis, pallor, dyspnea, nausea, and anxiety attacks.

Diagnosis uses increased urinary catecholamines, urinary fractional metanephrine, urinary VMA, and plasma free metanephrine (a negative plasma free metanephrine reliably excludes the tumor). Chromogranin A and methoxytyramine may be useful.

Clonidine suppresses sympathetic norepinephrine release via central α2 receptors but not tumor catecholamine release. After oral clonidine (4.3 µg/kg) given after fasting, blood is sampled at 3 hours for plasma catecholamines and normetanephrine. A positive test: failure to suppress norepinephrine >50% and normetanephrine >40% below baseline, with elevated levels at 3 hours. [pages 7–8]

Neuroblastoma is a malignant tumor derived from neural crest precursors that overproduce catecholamines and their metabolites. It occurs exclusively in children, accounting for 7–10% of childhood cancers and is the most common malignancy in the first year of life.

They most commonly arise in the abdomen (often adrenal gland); less frequently in chest, neck, and pelvis. Metastasis may involve bone marrow, bone, lymph nodes, liver, and less often skin, testis, and intracranial structures.

Hypertension and catecholamine‑excess signs are uncommon. Patients often present with an intra‑abdominal mass, compression symptoms on neighboring structures, and hematological abnormalities from bone marrow infiltration.

Neuroblastoma cells produce dopamine and norepinephrine (not epinephrine). Lab findings: elevated urinary HVA, elevated VMA, and increased urinary free dopamine.

Carcinoid tumors are neuroendocrine tumors derived from enterochromaffin cells, most commonly in the GIT (64%) and respiratory tract (28%). They often affect adults (mean age ~63) and are usually asymptomatic until metastasis.

They can secrete serotonin, histamine, kallikrein, bradykinins, tachykinins, prostaglandins, chromogranin A, dopamine, and norepinephrine.

Carcinoid syndrome occurs when vasoactive substances (e.g., serotonin) are released into systemic circulation, usually after liver metastasis. Symptoms: flushing, diarrhea, bronchoconstriction, and right‑sided valvular heart disease. Occurs in <10% of carcinoid patients.

Increased urinary 5‑HIAA (free + conjugated), increased plasma/platelet serotonin, increased serum chromogranin A. Urinary CgA and 5‑HIAA correlate with tumor burden and are useful for monitoring. Other markers: neuron‑specific enolase, neuropeptide K, substance P.

A VIPoma is a rare pancreatic tumor from non‑β islet cells that secretes excess vasoactive intestinal peptide (VIP). It’s associated with Verner–Morrison syndrome (VMS) or WDHA syndrome: watery diarrhea, hypokalemia, achlorhydria. Often malignant (50–70%) and sometimes linked to MEN1.

Symptoms: prolonged watery diarrhea, flushing, lethargy, muscle weakness, vomiting, abdominal pain, dehydration. Diagnosis: elevated fasting VIP, secretory diarrhea >3 L/day, hypokalemia, hyperchloremic metabolic acidosis, and hypochlorhydria.

An insulinoma is an insulin‑secreting tumor of pancreatic β cells (usually benign). Whipple’s triad defines it: fasting hypoglycemia (<50 mg/dL), symptoms of hypoglycemia (neuroglycopenic), and prompt symptom relief after glucose administration.

Symptoms include sweating, confusion, blurred vision, seizures, palpitation, and other neuroglycopenic or adrenergic features.

A 72‑hour fasting suppression test is the gold standard. Diagnostic criteria: serum insulin ≥10 μU/mL (normal <6), glucose <50 mg/dL, and C‑peptide >2.5 ng/mL.

Classical '10% rules': 10% multiple, 10% malignant, 10% associated with MEN1, and 10% ectopic.

The document covers SIADH (inappropriate ADH secretion causing dilutional hyponatremia) and Diabetes Insipidus (DI) — both cranial (central) and nephrogenic types.

Causes include ectopic ADH production (e.g., small cell lung carcinoma), CNS disease (tumor, infection), seizures, stress, pulmonary disorders, drugs (anticonvulsants, antipsychotics, ACE inhibitors), and post‑surgical states. Biochemical features: dilutional hyponatremia, serum hypo‑osmolality (<270–280 mOsm/kg), urine osmolality >250 mOsm/kg, increased ADH, low renin. [pages 24–29]

Diagnosis requires plasma hypo‑osmolality <275 mOsm/kg and Na+ <130 mmol/L after excluding cardiac, hepatic, renal, thyroid, or adrenal causes; urine osmolality > plasma osmolality.

Types: central (cranial) DI — impaired ADH production (causes: congenital, trauma, infection, tumor, infiltration, alcohol) and nephrogenic DI — impaired renal response to ADH (causes: congenital, sickle cell, nephropathy, chronic pyelonephritis, ATN, obstructive uropathy, CKD, hypercalcemia, hypokalemia, drugs like lithium and demeclocycline). [pages 31–33]

After water deprivation, if plasma osmolality >295 mOsm/kg and urine osmolality <600 mOsm/kg, DI is present. Give 2 µg DDAVP IM: if urine osmolality rises >750 mOsm/kg → central DI; if urine osmolality remains <300 mOsm/kg → nephrogenic DI. A summary table of post‑dehydration and post‑DDAVP values is provided. [pages 34–36]

Multiple Endocrine Neoplasia syndromes are familial dominantly inherited disorders where ≥2 endocrine glands secrete inappropriately. MEN1 is due to mutation in the MENIN gene; MEN2 is due to mutation in the RET gene.

MEN1: parathyroid glands, pancreatic islet cells (gastrinomas, insulinomas, glucagonomas, VIPomas, pancreatic polypeptide tumors), and anterior pituitary. MEN2: medullary thyroid carcinoma, pheochromocytoma, and parathyroid adenoma/carcinoma.