Section 8.4: Thyroid, Adrenal, & Pituitary Disorders
Key Takeaways
- Subclinical thyroid states are characterized by abnormal TSH with normal free thyroid hormone levels; treat subclinical hypothyroidism if TSH is ≥ 10 mIU/L or in pregnancy.
- Treat thyroid storm sequentially with beta-blockers, thionamides, inorganic iodine (at least one hour after thionamide), and glucocorticoids; treat myxedema coma with IV thyroid hormone and hydrocortisone.
- Diagnose primary adrenal insufficiency via morning cortisol and a cosyntropin stimulation test; treat with glucocorticoids and mineralocorticoids, adjusting for stress.
- Screen for Cushing syndrome with overnight dexamethasone suppression, late-night salivary cortisol, or 24-hour urine cortisol; localize via ACTH levels and high-dose suppression.
- Hyperprolactinemia is treated first-line with dopamine agonists like cabergoline; transsphenoidal surgery is reserved for drug-refractory cases or progressive visual field deficits.
Hyperthyroidism and Hypothyroidism: Diagnosis and Subclinical States
Thyroid disorders are common clinical entities requiring systematic laboratory evaluation. Primary hyperthyroidism is characterized by a suppressed thyroid-stimulating hormone (TSH) level and elevated free thyroxine (T4) and/or free triiodothyronine (T3). The etiology is determined by radioactive iodine uptake (RAIU) scanning:
- Graves Disease: Demonstrates diffuse, homogeneous uptake. It is caused by autoantibodies that stimulate the TSH receptor.
- Toxic Multinodular Goiter and Toxic Adenoma: Show heterogeneous uptake with multiple hot nodules or a single hot nodule, respectively, and suppression of the surrounding thyroid tissue.
- Thyroiditis (e.g., subacute de Quervain, postpartum, silent): Demonstrates low or absent RAIU due to release of preformed hormone. Subacute thyroiditis is painful, follows viral infection, and has elevated ESR.
Subclinical hyperthyroidism is defined by a low TSH with normal free T4 and T3 levels. Treatment is indicated in patients aged ≥ 65, postmenopausal women not taking estrogens, patients with cardiovascular disease or osteopenia/osteoporosis, or those with a TSH persistently < 0.1 mIU/L, to prevent atrial fibrillation and bone mineral density loss.
Primary hypothyroidism shows elevated TSH and low free T4. Hashimoto thyroiditis, characterized by anti-TPO antibodies, is the most common cause. Treat with levothyroxine (~1.6 mcg/kg/day); start at 25–50 mcg in elderly or coronary artery disease patients. Take on an empty stomach. Subclinical hypothyroidism is treated if TSH ≥ 10 mIU/L, or if pregnant, symptomatic, or has high anti-TPO antibodies.
Thyroid Emergencies: Thyroid Storm and Myxedema Coma
Thyroid storm is a life-threatening hypermetabolic state precipitated by infection, trauma, surgery, or iodine exposure in patients with unrecognized or poorly controlled hyperthyroidism. Clinical manifestations include severe hyperthermia, marked tachycardia, agitation, delirium, high-output heart failure, and jaundice. Management requires a specific sequential therapeutic protocol to block thyroid hormone synthesis, release, and peripheral conversion:
- Beta-blockade: Intravenous or oral propranolol to control adrenergic activity and inhibit peripheral T4-to-T3 conversion.
- Thionamides: Propylthiouracil (PTU) is preferred over methimazole in storm because it blocks both thyroid hormone synthesis and the peripheral conversion of T4 to T3.
- Inorganic Iodine: Administer Lugol's solution or potassium iodide. Critical timing: Iodine must be administered at least 1 hour after thionamide administration to prevent the iodine from being used as a substrate for new thyroid hormone synthesis (Wolff-Chaikoff effect).
- Glucocorticoids: Intravenous hydrocortisone or dexamethasone to inhibit peripheral conversion of T4 to T3 and treat potential relative adrenal insufficiency.
- Supportive Care: Cooling blankets (avoid aspirin as it displaces thyroid hormone from thyroid-binding globulin) and IV fluids.
Myxedema coma is a life-threatening complication of severe hypothyroidism, presenting with hypothermia, bradycardia, hypotension, hypoventilation, and altered mental status. Treatment involves immediate administration of intravenous levothyroxine (T4) and liothyronine (T3), supportive warming, and intravenous hydrocortisone. Hydrocortisone must be administered prior to or concurrently with thyroid hormone replacement to avoid precipitating an acute adrenal crisis in patients with unrecognized concurrent adrenal insufficiency (Schmidt syndrome).
Adrenal Insufficiency and Cushing Syndrome
Primary adrenal insufficiency (Addison disease) results from destruction of the adrenal cortex, leading to glucocorticoid, mineralocorticoid, and androgen deficiencies. The most common cause in developed countries is autoimmune adrenalitis; infectious causes (tuberculosis, cytomegalovirus) predominate in developing countries or immunocompromised hosts. Patients present with fatigue, weight loss, hyperpigmentation (due to ACTH-stimulated melanocyte-stimulating hormone co-secretion), hyponatremia, and hyperkalemia (due to aldosterone deficiency).
Diagnosis is established via:
- Morning Serum Cortisol: A level < 3 mcg/dL suggests adrenal insufficiency, while a level > 19 mcg/dL rules it out.
- Cosyntropin Stimulation Test: Standard diagnostic test. Measure serum cortisol 30 and 60 minutes after administration of 250 mcg of synthetic ACTH. A peak cortisol level < 18 mcg/dL confirms adrenal insufficiency.
- Plasma ACTH: Elevated in primary adrenal insufficiency and low/normal in secondary adrenal insufficiency (hypopituitarism, where mineralocorticoid function is preserved).
Maintenance therapy requires glucocorticoid replacement (hydrocortisone or prednisone) and mineralocorticoid replacement (fludrocortisone). During periods of minor illness, patients must double or triple their oral glucocorticoid dose ("stress dosing"); major illness or surgery requires intravenous hydrocortisone (100 mg). Adrenal crisis (profound hypotension, hypoglycemia, hyperkalemia) is treated immediately with high-dose IV hydrocortisone and aggressive crystalloid resuscitation.
Cushing syndrome (hypercortisolism) screening requires at least two positive first-line tests: 24-hour urine free cortisol, late-night salivary cortisol, or the overnight 1-mg dexamethasone suppression test (normal is suppression of morning cortisol to < 1.8 mcg/dL). Once hypercortisolism is confirmed, plasma ACTH distinguishes ACTH-independent causes (adrenal adenoma/carcinoma; ACTH < 5 pg/mL) from ACTH-dependent causes (pituitary Cushing disease or ectopic ACTH secretion; ACTH > 20 pg/mL). High-dose (8-mg) dexamethasone suppression and CRH stimulation tests help differentiate Cushing disease (which typically suppresses cortisol by > 50% and responds to CRH) from ectopic sources.
Hyperprolactinemia
Hyperprolactinemia is caused by prolactin-secreting pituitary adenomas (prolactinomas), drugs that block dopamine receptors (antipsychotics, metoclopramide), or stalk compression (which loss of dopamine's tonic inhibition). Patients present with galactorrhea, hypogonadotropic hypogonadism (amenorrhea, erectile dysfunction), and visual field defects (bitemporal hemianopsia) in macroadenomas (> 10 mm). First-line therapy for prolactinomas is medical with dopamine agonists, specifically cabergoline (preferred due to high efficacy and tolerability) or bromocriptine. Surgery is reserved for patients refractory to medical management or those with progressive neurological deficits.
A 32-year-old woman is admitted to the hospital due to high fever, confusion, and extreme agitation. She has a history of Graves disease but has been non-adherent to her medications. Her temperature is 39.8°C (103.6°F), blood pressure is 142/88 mmHg, and heart rate is 144/min. She is noted to have a diffuse goiter and mild proptosis. After starting intravenous fluids and cooling blankets, what is the most appropriate sequence of pharmacotherapy?
A 40-year-old woman presents with worsening fatigue, generalized weakness, and a 6-kg weight loss over the past four months. On examination, she has hyperpigmentation of her palmar creases and oral mucosa. Her blood pressure is 92/58 mmHg, and heart rate is 88/min. Laboratory studies show: serum sodium 128 mEq/L, potassium 5.6 mEq/L, and morning serum cortisol 2.4 mcg/dL. What is the most appropriate next step to confirm the diagnosis?
A 28-year-old woman is evaluated for amenorrhea and milky breast discharge of six months' duration. She is not pregnant and takes no medications. Her physical examination is normal, with no visual field defects. Laboratory studies show a serum prolactin level of 180 ng/mL (normal < 25 ng/mL). A brain MRI reveals a 6-mm pituitary lesion. Which of the following is the most appropriate initial management?