12.2 Thyroid & Parathyroid Disorders
Key Takeaways
- Primary hypothyroidism presents with elevated TSH and low free T4, with Hashimoto thyroiditis (anti-TPO antibodies) being the leading etiology in developed nations.
- Thyroid storm requires sequential treatment with beta-blockers, propylthiouracil (PTU) or methimazole, potassium iodide (given ≥1 hour post-antithyroid drug), and hydrocortisone.
- A thyroid nodule with normal/high TSH requires ultrasound; nodules ≥1 cm with high-risk ultrasound features (microcalcifications, hypoechoic, irregular margins) warrant Fine Needle Aspiration (FNA).
- Primary hyperparathyroidism exhibits hypercalcemia, elevated or inappropriately normal PTH, hypophosphatemia, and 24-hour urine calcium clearance >0.01.
- Severe hypercalcemia (>14 mg/dL) requires immediate aggressive intravenous 0.9% normal saline hydration followed by calcitonin and bisphosphonates (zoledronic acid).
Thyroid & Parathyroid Disorders
Thyroid Physiology and Diagnostic Testing Interpretation
Thyroid hormone production is regulated by the hypothalamic-pituitary-thyroid axis via Thyrotropin-Releasing Hormone (TRH) and Thyroid-Stimulating Hormone (TSH). Serum TSH is the most sensitive screening test for thyroid dysfunction due to an inverse logarithmic relationship with free thyroid hormone levels.
Interpretation of Thyroid Function Profiles
| Clinical Condition | TSH Level | Free T4 Level | Free T3 Level | Clinical Features & Diagnostic Clues |
|---|---|---|---|---|
| Primary Hypothyroidism | Elevated (>4.5 mIU/L) | Low | Low or Normal | Fatigue, weight gain, cold intolerance, constipation, dry skin, delayed relaxation of deep tendon reflexes. Most common cause: Hashimoto thyroiditis (anti-TPO and anti-thyroglobulin antibodies positive). |
| Subclinical Hypothyroidism | Elevated (>4.5 mIU/L) | Normal | Normal | Asymptomatic or mild symptoms. Treat if TSH >10 mIU/L, positive anti-TPO antibodies, symptomatic, pregnant, or presence of goiter. |
| Primary Hyperthyroidism | Suppressed (<0.1 mIU/L) | Elevated | Elevated | Weight loss, heat intolerance, tremor, palpitations, anxiety, frequent bowel movements. Causes: Graves disease (TSI/TRAb positive, diffuse RAIU), Toxic Multinodular Goiter, Toxic Adenoma. |
| Subacute (de Quervain) Thyroiditis | Suppressed (<0.1 mIU/L) | Elevated (Early) | Elevated (Early) | Painful, tender thyroid goiter, post-viral prodrome, elevated ESR/CRP, markedly low radioactive iodine uptake (RAIU). |
| Central Hypothyroidism | Low or Normal | Low | Low | Secondary (pituitary) or tertiary (hypothalamic) failure. Accompanied by other anterior pituitary hormone deficiencies. |
Diagnostic Algorithm for Thyroid Nodules and Malignancy
Thyroid nodules are detected in up to 65% of the general population. The diagnostic goal is distinguishing benign nodules from thyroid carcinomas (papillary, follicular, medullary, anaplastic).
[ Solitary Thyroid Nodule Discovered ]
│
[ Measure Serum TSH ]
│
┌──────────────────────────────┴──────────────────────────────┐
[ Low TSH (Hyperthyroid) ] [ Normal or High TSH ]
│ │
[ Iodine-123 Scintigraphy ] ▼
│ [ Thyroid Ultrasound ]
┌────────┴────────┐ │
▼ ▼ ┌─────────────┴─────────────┐
["Hot" Nodule] ["Cold" Nodule] │ │
(Hyperfunctioning) (Non-functioning) [ High-Risk Features ] [ Benign Features ]
│ │ (≥1 cm, microcalcif, (purely cystic,
▼ └──────────────────────────────► hypoechoic, solid) sponge-like)
Evaluate for │ │
Hyperthyroidism ▼ ▼
(Low malignancy) [ FNA Biopsy ] [ Clinical Monitoring ]
Risk Stratification for Fine Needle Aspiration (FNA)
- FNA Biopsy Indicated:
- Nodules ≥1.0 cm with high-risk sonographic features (microcalcifications, hypoechoic texture, irregular margins, taller-than-wide shape, or extrathyroidal extension).
- Nodules ≥1.5 cm with intermediate-risk features (hypoechoic solid nodules with smooth margins).
- Nodules ≥2.0 cm with low-risk features (isoechoic or hyperechoic solid nodules).
- Cytological Classification (Bethesda System):
- Papillary Thyroid Carcinoma: Most common (80–85%). Histology displays Orphan Annie eye nuclei, psammoma bodies, and nuclear grooves. Excellent prognosis. Lymphatic spread.
- Follicular Thyroid Carcinoma: Requires capsular or vascular invasion to distinguish from follicular adenoma (FNA cannot distinguish; requires surgical excision). Hematogenous spread.
- Medullary Thyroid Carcinoma: Derived from parafollicular C-cells; secretes calcitonin. Associated with MEN 2A and 2B (RET proto-oncogene mutation). Histology displays amyloid stroma (Congo red positive).
- Anaplastic Thyroid Carcinoma: Elderly patients, rapidly enlarging painful neck mass, compressive symptoms (dysphagia, hoarseness). Extremely aggressive, fatal.
Thyroid Emergencies: Thyroid Storm & Myxedema Coma
- Thyroid Storm: Life-threatening hypermetabolic state triggered by surgery, infection, trauma, or iodine load in uncontrolled hyperthyroidism. Features include high fever (>104°F/40°C), severe tachycardia/atrial fibrillation, agitation, delirium, vomiting, diarrhea, and jaundice.
- Management Multimodal Protocol:
- Beta-Blocker: Intravenous Propranolol (blocks sympathetic surge and peripheral T4-to-T3 conversion).
- Antithyroid Drug: Propylthiouracil (PTU) or Methimazole (inhibits thyroid peroxidase; PTU preferred in thyroid storm as it also blocks peripheral T4-to-T3 conversion).
- Iodine Solution: Lugol's iodine or Potassium Iodide (SSKI) administered at least 1 hour AFTER antithyroid medication to prevent iodine from serving as substrate for new hormone synthesis (Wolff-Chaikoff effect).
- Glucocorticoids: Hydrocortisone IV (blocks peripheral conversion of T4 to T3 and treats relative adrenal insufficiency).
- Management Multimodal Protocol:
- Myxedema Coma: Severe end-stage hypothyroidism presenting with hypothermia, bradycardia, hypoventilation, hyponatremia, and altered mental status. Treatment involves IV Levothyroxine (T4) plus IV Hydrocortisone (to prevent adrenal crisis if coexisting adrenal insufficiency is present).
Parathyroid Disorders & Calcium Homeostasis
Calcium homeostasis is tightly regulated by Parathyroid Hormone (PTH), 1,25-dihydroxyvitamin D (calcitriol), and calcitonin. PTH increases serum calcium by increasing bone resorption, enhancing renal distal tubule calcium reabsorption, and stimulating 1-alpha-hydroxylase in the kidney to synthesize active Vitamin D.
| Disorder | Serum Calcium | Serum Phosphate | Serum PTH | 24-Hour Urine Calcium | Key Clinical Features & Management |
|---|---|---|---|---|---|
| Primary Hyperparathyroidism | Elevated | Low or Normal | Elevated or Inappropriate Normal | Elevated (>250 mg/day; Ca clearance ratio >0.01) | Parathyroid adenoma (85%). "Stones, bones, abdominal groans, psychiatric overtones." Subperiosteal bone resorption. Surgery indicated if age <50, Ca >1.0 mg/dL above normal, eGFR <60, or T-score <-2.5. |
| Familial Hypocalciuric Hypercalcemia (FHH) | Elevated | Normal or Low | Normal or Slightly Elevated | Low (Urine Ca clearance ratio <0.01) | Inactivating mutation of Calcium-Sensing Receptor (CaSR). Benign condition; surgery is contraindicated. |
| Hypercalcemia of Malignancy | Elevated | Low or High | Suppressed (<10 pg/mL) | Elevated | 1. PTHrP secretion (squamous cell lung, renal, head/neck). 2. Osteolytic metastases (breast, multiple myeloma). 3. 1,25-OH2 Vit D excess (lymphoma, sarcoidosis). |
| Hypoparathyroidism | Low | Elevated | Low or Undetectable | Low | Postsurgical removal/damage during thyroidectomy (most common). Signs: Chvostek sign (facial twitching), Trousseau sign (carpopedal spasm), prolonged QT. Tx: Oral Ca + Calcitriol. Emergency: IV Calcium Gluconate. |
Emergency Management of Severe Hypercalcemia (>14 mg/dL or Symptomatic)
- Intravenous Hydration: Administer aggressive IV 0.9% Normal Saline (200–500 mL/hr) to restore intravascular volume and promote renal calcium excretion.
- Calcitonin: Administer subcutaneous/IV calcitonin for rapid lowering of serum calcium within 2–4 hours (inhibits osteoclast activity; limited by tachyphylaxis after 48 hours).
- Bisphosphonates: Infuse Zoledronic acid or Pamidronate for long-term inhibition of bone resorption (onset of action in 2–4 days). Calcitonin serves as a bridge until bisphosphonates take effect.
A 32-year-old woman with a history of poorly controlled Graves disease is admitted to the intensive care unit following an emergency appendectomy. She is febrile to 104.2°F (40.1°C), tachycardic to 154/min with atrial fibrillation, agitated, and vomiting. Laboratory studies show a TSH <0.01 mIU/L and free T4 of 4.8 ng/dL. Intravenous propranolol and propylthiouracil are administered. Which of the following is the most appropriate next step in pharmacological management?
A 46-year-old woman is evaluated during a routine health maintenance exam. Serum laboratory studies demonstrate a calcium level of 11.2 mg/dL, phosphate of 2.2 mg/dL, and parathyroid hormone (PTH) level of 92 pg/mL (normal 15-65 pg/mL). A 24-hour urine collection reveals a urinary calcium excretion of 340 mg/24 hr, with a calculated calcium-to-creatinine clearance ratio of 0.025. Dual-energy X-ray absorptiometry (DEXA) scan shows a T-score of -2.7 at the lumbar spine. Which of the following is the most appropriate next step in management?
A 52-year-old man is found to have a 1.4-cm solitary nodule in the right thyroid lobe on physical examination. Serum TSH level is 2.1 mIU/L (normal). Thyroid ultrasound demonstrates a 1.4-cm solid, hypoechoic nodule with punctate microcalcifications and irregular margins in the right thyroid lobe. Which of the following is the most appropriate next step in management?