Why are a comprehensive metabolic panel, complete blood count, serum prolactin, liver function tests, and creatine kinase recommended for evaluating complications of untreated hypothyroidism?

Why Check These Labs for Hypothyroid Complications?

Your professor is teaching you to screen for the systemic complications of untreated or poorly controlled hypothyroidism, which can affect multiple organ systems and cause serious morbidity if missed.

Comprehensive Metabolic Panel (CMP) for Hyponatremia

Hypothyroidism directly causes hyponatremia through impaired free water clearance and inappropriate ADH secretion. 1

• Untreated hypothyroidism reduces cardiac output and renal blood flow, leading to decreased glomerular filtration and impaired water excretion 1
• The metabolic slowing affects kidney function, causing sodium dilution even without true sodium depletion 1
• Hyponatremia can manifest as confusion, weakness, or altered mental status—symptoms that overlap with hypothyroidism itself, making it critical to identify 2
• Severe hyponatremia is a risk factor for myxedema coma, which carries up to 30% mortality 2

The CMP also screens for other metabolic derangements including hyperglycemia (hypothyroidism causes insulin resistance) and renal dysfunction 2

Complete Blood Count (CBC) for Anemia

Hypothyroidism commonly causes normocytic or macrocytic anemia through multiple mechanisms. 1

• The reduced metabolic rate decreases erythropoietin production and bone marrow activity 1
• Autoimmune hypothyroidism (Hashimoto's) frequently coexists with pernicious anemia (anti-parietal cell antibodies), causing B12 deficiency and macrocytic anemia 1
• Iron deficiency anemia occurs from menorrhagia, which affects approximately 23% of women with hypothyroidism 2
• Anemia contributes to the fatigue that affects 68-83% of hypothyroid patients, and treating the thyroid alone may not resolve symptoms if concurrent anemia exists 2

Serum Prolactin

Hypothyroidism causes hyperprolactinemia through loss of negative feedback on the pituitary. 1

• Low thyroid hormone levels trigger increased TRH (thyrotropin-releasing hormone) from the hypothalamus 1
• TRH stimulates both TSH and prolactin release from the pituitary 1
• Elevated prolactin causes menstrual irregularities (oligomenorrhea, amenorrhea), galactorrhea, and infertility—symptoms that may be the presenting complaint 2, 1
• Checking prolactin helps distinguish whether menstrual dysfunction is from hypothyroidism alone or requires additional evaluation for pituitary pathology 1

Liver Function Tests (LFTs)

Hypothyroidism causes hepatic dysfunction with elevated transaminases and alkaline phosphatase. 1

• The metabolic slowing reduces hepatic clearance of enzymes and metabolites 1
• Mild transaminase elevations (AST, ALT) occur from decreased hepatic metabolism 1
• Alkaline phosphatase may be elevated from both hepatic and bone sources 1
• Severe hypothyroidism can cause non-alcoholic fatty liver disease (NAFLD) 1
• Abnormal LFTs may prompt unnecessary hepatic workup if hypothyroidism isn't recognized as the cause 1

Creatine Kinase (CK) Levels

Hypothyroid myopathy causes marked CK elevation, sometimes reaching levels seen in inflammatory myopathies or muscular dystrophies. 3

• CK elevations occur in the majority of hypothyroid patients, though usually modest 3
• Rare cases show CK levels exceeding 29,000 IU/L—high enough to mimic rhabdomyolysis, polymyositis, or dystrophy 3
• The mechanism involves impaired muscle metabolism, reduced enzyme clearance, and direct myopathic changes 3
• Patients present with proximal muscle weakness, myalgias, and muscle stiffness 3
• Critical pitfall: Failing to check TSH in patients with elevated CK and weakness can lead to extensive (and unnecessary) neuromuscular workup including muscle biopsy, when the cause is simply hypothyroidism 3
• Thyroid hormone replacement resolves the myopathy and normalizes CK levels within weeks to months 3

Clinical Integration

These labs form a systematic screen for the multi-organ complications of hypothyroidism that directly impact morbidity and quality of life. 4, 2

• Untreated hypothyroidism causes heart failure, dyslipidemia, cognitive impairment, infertility, and in severe cases, myxedema coma with 30% mortality 4, 2
• The consequences are reversible with levothyroxine treatment, but only if recognized 4
• Checking these labs at diagnosis establishes baseline abnormalities that should improve with treatment 5
• Persistent abnormalities despite normalized TSH suggest either inadequate treatment or coexisting conditions requiring separate management 5

In pregnant women, these complications become even more critical—untreated hypothyroidism causes cognitive deficits in children, preterm birth, placental abruption, and fetal death. 4