12.3 Endocrine Pathology: Pancreas, Adrenal, Parathyroid, Thyroid & Pituitary Disorders

Why this area matters

The TOS lists "disorders of the pancreas, adrenals, parathyroid, thyroid glands, pituitary gland". Diabetes is a major cause of kidney failure, blindness and amputation in the Philippines. Goiter remains common in iodine-deficient areas, and thyroid nodules are frequent clinical problems.

Endocrine pancreas

Chronic complications:

• Macrovascular: accelerated atherosclerosis, causing MI, stroke and gangrene.
• Microvascular: hyaline arteriolosclerosis.
• Nephropathy: nodular glomerulosclerosis (Kimmelstiel-Wilson nodules).
• Retinopathy: non-proliferative microaneurysms progressing to proliferative neovascularization.
• Neuropathy: symmetric sensory "glove-and-stocking" loss, plus autonomic neuropathy.
• Infections.

The mechanisms are non-enzymatic glycation (advanced glycation end-products; HbA1c as a marker), the polyol pathway (sorbitol, which also causes cataracts), protein kinase C activation and oxidative stress.

Pancreatic neuroendocrine tumors:

• insulinoma, the most common: Whipple triad of hypoglycemia, symptoms and relief with glucose, with high C-peptide;
• gastrinoma (Zollinger-Ellison syndrome);
• glucagonoma: necrolytic migratory erythema and diabetes;
• VIPoma: watery diarrhea, hypokalemia, achlorhydria.

These may be part of MEN1 (pituitary, parathyroid and pancreatic tumors).

Adrenal gland

• Cushing syndrome (hypercortisolism): central obesity, moon face, buffalo hump, purple striae, hypertension, hyperglycemia, osteoporosis, immunosuppression.
  • Exogenous glucocorticoids: the most common cause; the adrenals are atrophic.
  • Pituitary ACTH adenoma (Cushing disease): high ACTH, bilateral adrenal hyperplasia, suppresses with high-dose dexamethasone.
  • Ectopic ACTH (small cell lung carcinoma): very high ACTH, does not suppress, often hypokalemia.
  • Adrenal adenoma or carcinoma: low ACTH, atrophy of the opposite adrenal.
• Primary hyperaldosteronism (Conn syndrome): usually an adenoma or bilateral hyperplasia. It causes hypertension, hypokalemia and metabolic alkalosis, with high aldosterone and low renin.
• Congenital adrenal hyperplasia: 21-hydroxylase deficiency is the most common. Low cortisol and aldosterone with excess androgens cause virilization of girls (ambiguous genitalia) and salt-wasting crises in newborns. Raised 17-hydroxyprogesterone is detected on newborn screening.
• Adrenal insufficiency:
  • Acute: adrenal crisis after steroid withdrawal, or Waterhouse-Friderichsen syndrome (bilateral adrenal hemorrhage in meningococcemia).
  • Chronic primary (Addison disease): autoimmune (the most common cause in developed countries), tuberculosis (important in the Philippines) or metastases. Hyperpigmentation (high ACTH/MSH), hypotension, hyponatremia and hyperkalemia.
  • Secondary insufficiency (from the pituitary) lacks hyperpigmentation and hyperkalemia.
• Pheochromocytoma: a tumor of the adrenal medulla that secretes catecholamines. It causes episodic headache, sweating, palpitations and hypertension.
  • "Rule of 10s" (approximate): extra-adrenal, bilateral, malignant, familial, in children.
  • Diagnosis is by plasma or urinary metanephrines. Histology shows "zellballen" nests that are chromogranin positive.
  • Associated syndromes are MEN2A and 2B, VHL and NF1.
• Neuroblastoma: a medullary tumor of children; discussed in Pediatrics.

Parathyroid glands and calcium

• Primary hyperparathyroidism:
  • About 85% to 90% of cases come from a single adenoma; the rest from hyperplasia (MEN1, MEN2A) or, rarely, carcinoma.
  • Findings are high calcium, high PTH and low phosphate, summed up as "stones, bones, groans and psychiatric overtones".
  • Kidney stones and nephrocalcinosis may develop.
  • Osteitis fibrosa cystica includes brown tumors and subperiosteal resorption of the phalanges.
  • Most cases are found on routine calcium screening.
• Secondary hyperparathyroidism: a response to low calcium, mainly in chronic kidney disease (phosphate retention, low calcitriol) or vitamin D deficiency. Calcium is low or normal, PTH is high and phosphate is high in CKD. It causes renal osteodystrophy.
• Hypoparathyroidism: usually after thyroid surgery, also autoimmune or DiGeorge syndrome. It causes hypocalcemia with tetany (Chvostek and Trousseau signs) and a prolonged QT.
• Hypercalcemia of malignancy: PTHrP (squamous cell carcinomas), osteolytic metastases or myeloma; PTH is suppressed.

Thyroid gland

Thyroiditis:

• Hashimoto thyroiditis: the most common cause of hypothyroidism where iodine is sufficient. Lymphocytes with germinal centers, Hurthle (oncocytic) cells and anti-TPO and anti-thyroglobulin antibodies. Raises the risk of B-cell (MALT) lymphoma.
• Subacute granulomatous (de Quervain) thyroiditis: follows a viral infection. Painful gland, transient hyperthyroidism, high ESR, granulomas.
• Riedel thyroiditis: dense fibrosis (IgG4-related), with a hard gland.

Goiter:

• Diffuse and multinodular goiter from iodine deficiency is endemic in some Philippine areas. It may produce a toxic nodule (Plummer disease).
• Graves disease: IgG antibodies stimulate the TSH receptor. It causes hyperthyroidism, a diffuse goiter, ophthalmopathy (exophthalmos) and pretibial myxedema. Histology shows tall hyperplastic follicles with scalloped, pale colloid.

Thyroid carcinomas:

Pituitary gland

• Adenomas:
  • Prolactinoma, the most common: galactorrhea and amenorrhea in women, low libido in men; treated with dopamine agonists.
  • Somatotroph adenoma: gigantism or acromegaly.
  • Corticotroph adenoma: Cushing disease.
  • Macroadenomas (larger than 1 cm) cause bitemporal hemianopia and hypopituitarism.
• Hypopituitarism:
  • Sheehan syndrome is postpartum pituitary necrosis after massive obstetric hemorrhage. The first sign is failure to lactate.
  • Other causes are pituitary apoplexy, tumors, surgery or radiation, and craniopharyngioma in children (calcified suprasellar cystic tumor from Rathke pouch remnants).
• Posterior pituitary:
  • Central diabetes insipidus (deficient ADH: trauma, surgery, tumors) causes polyuria with dilute urine that responds to desmopressin.
  • SIADH (small cell carcinoma, CNS disease, drugs) causes euvolemic hyponatremia with concentrated urine.