Ms. G, age 56, presents with the chief complaint of “depression.” Review of symptoms reveals 6 months of depressed mood, anhedonia, tearfulness, 30-pound weight gain, low energy, and bilateral ankle edema. Her psychiatrist orders a thyroid stimulating hormone (TSH) level, which shows 9.51 mU/L (normal range 0.35 to 4.94 mU/L), indicating hypothyroidism. After 1 month of treatment with levothyroxine, Ms. G’s mood symptoms and edema resolve and her weight stabilizes.
A patient who comes to you for treatment of depression might also present with physical symptoms (such as, fatigue, nausea, balance problems, etc.) that could point to a medical illness. Endocrine, neurologic, infectious, and malignant processes (Table 1) and vitamin deficiencies (Table 2) could be causing your patient’s depression. To help differentiate various etiologies of depressive symptoms, we review common medical causes of depression, their distinguishing characteristics, and pertinent treatment issues.
DSM-IV-TR considers major depression secondary to a general medical condition to be diagnostically separate from a major depressive episode. When considering nonpsychiatric causes of depression, begin with a thorough medical history including current and past medications (Table 3),1-7 illicit substance use, review of systems, and a detailed neurologic exam.
Table 1
Medical conditions with evidence of causing depression
| Endocrine Hypothyroidism Hyperparathyroidism Cushing’s syndrome Addison’s disease |
| Neurologic Stroke Seizures Huntington’s disease Wilson’s disease Multiple sclerosis Parkinson’s disease Traumatic brain injury |
| Infectious Human immunodeficiency virus West Nile virus Creutzfeldt-Jakob disease Lyme disease Neurosyphilis Hepatitis C |
| Malignancy Paraneoplastic syndromes Pancreatic cancer |
Table 2
Vitamin deficiencies that can lead to depression
| Vitamin | Symptom |
|---|---|
| B12 | Megaloblastic anemia Decreased appetite Unexplained pancytopenia Paresthesias Dementia Glossitis Depressed mood Ataxia Irritability |
| Folate | Ataxia Depressed mood Dementia Impaired vibratory sensation Hyper- or hyporeflexia Macrocytic anemia |
Table 3
Medications that may be linked to depressive symptoms
| Antiepileptic drugs Primidone, tiagabine, vigabatrin, felbamate, levetiracetam, topiramate, and phenytoin may cause depression,1 and phenobarbital may cause depression associated with suicidal ideation2 |
| Beta-blockers Recent randomized studies indicate these drugs do not carry a higher risk of depression, contrary to earlier accepted wisdom |
| Corticosteroids Depressive symptoms may occur after initial corticosteroid administration, with long-term use, or with drug discontinuation3 |
| Interferon alfa Depression rates of nearly 50% have been reported.4 Depressive symptoms seem to be related to dose and duration of treatment and may take several weeks to develop |
| Interferon beta Initial studies raised concern about an increased risk of depression and suicide, but a review of 16 studies did not detect an increased risk of depression5 |
| Isotretinoin Although initial studies did not show an association between isotretinoin and depression and suicide, 24 reports of depression and more than 170 cases of isotretinoin-associated suicide have been reported.6 In many patients, depressive symptoms resolved when the medication was discontinued, and several case studies reported depression recurrence with medication rechallenge |
| Varenicline and bupropion Postmarketing cases have described neuropsychiatric symptoms including depression and suicidal ideation with these antismoking agents, prompting changes in the drugs’ prescribing information. Many of the cases reflect new-onset depressed mood, suicidal ideation, and changes in emotion and behavior within days to weeks of initiating treatment. Patients with pre-existing psychiatric illness may experience worsening of symptoms7 |
Endocrine disorders
Hypothyroidism increases a patient’s risk of a mood disorder 7-fold, compared with the general population.8
Signs and symptoms. Patients with hypothyroidism may complain of constipation, thinning hair, dry skin, edema, sensitivity to cold, goiter, thyroid nodule, or hoarse voice. Symptoms such as fatigue, weight gain, and sleep disturbance overlap with depressive symptoms. A TSH value >4.94 mU/L indicates hypothyroidism and warrants referral to a primary care provider or endocrinologist.
Although the pathophysiology is unclear, 1 study found elevated thyroid peroxide antibodies in depressed postmenopausal women who had abnormal thyroid function tests, suggesting an autoimmune link between depression and hypothyroidism.9 In another study, 2.5% of depressed patients had abnormal serum TSH or thyroxine levels indicating hypothyroidism.10 Thyroid hormones have been used to augment treatment of refractory depression.11
Hyperparathyroidism. “Moans, groans, stones, and psychiatric overtones” describes the constellation of hyperparathyroidism symptoms. As serum calcium levels rise, mood and physical symptoms worsen (Table 4).
Signs and symptoms. Elevated serum calcium (normal range 8.7 to 10.7 mg/dL) and parathyroid hormone (PTH) levels support the diagnosis. Depressive symptoms may diminish or even resolve when calcium levels return to normal after parathyroidectomy.12
Cushing’s syndrome (CS). As many as 80% of patients exhibit depressive symptoms when CS is active.13
Signs and symptoms. Distinguishing CS symptoms include:
- hirsutism
- truncal obesity
- acne
- hypertension
- facial flushing
- purple striae.
Elevated serum cortisol, the condition’s hallmark, may be caused by pituitary adenomas, adrenal tumors or hyperplasia, or ectopic adrenocorticotropic hormone secretion. The most common cause is exogenous administration of glucocorticoids. A dexamethasone suppression test or 24-hour urine cortisol confirms CS diagnosis.