What other diseases can present with both chronic constipation and hypothyroidism in a patient whose constipation began before starting amlodipine?

Differential Diagnosis: Diseases Presenting with Both Chronic Constipation and Hypothyroidism

The key diseases to consider when a patient presents with both chronic constipation and hypothyroidism include autoimmune polyglandular syndromes (particularly type 1 diabetes mellitus and systemic lupus erythematosus), mitochondrial disorders (especially MNGIE), connective tissue diseases (particularly scleroderma), and celiac disease—all of which can coexist with Hashimoto's thyroiditis and cause gastrointestinal dysmotility independent of thyroid dysfunction. 1, 2, 3

Primary Autoimmune Associations

Type 1 Diabetes Mellitus

• Type 1 diabetes is a common autoimmune comorbidity in Hashimoto's thyroiditis patients and can independently cause chronic constipation through diabetic autonomic neuropathy affecting the enteric nervous system 1
• This represents an autoimmune polyglandular syndrome where multiple endocrine organs are affected simultaneously 1, 3

Systemic Lupus Erythematosus (SLE)

• SLE is associated with Hashimoto's thyroiditis and can cause intestinal pseudo-obstruction through vasculitis or smooth muscle dysfunction 1
• The gastrointestinal manifestations may precede or follow the thyroid diagnosis by years 3

Celiac Disease

• Celiac disease has been implicated in some cases of dysmotility and frequently coexists with autoimmune thyroid disease 2, 3
• Screen with anti-tissue transglutaminase antibodies in patients with both constipation and hypothyroidism 2

Connective Tissue Disorders

Scleroderma (Systemic Sclerosis)

• Scleroderma can cause both hypothyroidism and severe gastrointestinal dysmotility through fibrosis of the thyroid gland and intestinal smooth muscle 2
• Screen with anti-centromere, anti-Scl70, and anti-M3R antibodies 2
• The gastrointestinal involvement in scleroderma is often more severe than thyroid dysfunction alone would explain 2

Mitochondrial Disorders

MNGIE (Mitochondrial Neurogastrointestinal Encephalomyopathy)

• MNGIE is the most common mitochondrial disorder causing severe gastrointestinal dysmotility and can present with chronic constipation, bacterial overgrowth, and cachexia 2
• Patients typically present between ages 18-37 years with progressive symptoms including ophthalmoplegia (91%), polyneuropathy (96%), and leukoencephalopathy (96%) 2
• Screen with plasma and urine thymidine and deoxyuridine levels, white blood cell thymine phosphorylase, and TYMP gene testing 2
• This diagnosis is critical as it carries a poor prognosis with mean survival of 37.6 years 2

Paraneoplastic Syndromes

Small Cell Lung Carcinoma and Thymoma

• Paraneoplastic neuropathy from small cell carcinoma or thymoma can cause both enteric neuropathy (presenting as constipation) and autoimmune thyroid dysfunction 2
• Screen with chest X-ray or CT/PET-CT and test for ANNA-1 (anti-Hu), anti-CRMP-5, ganglionic acetylcholine receptor antibodies, and anti-VGKC-complex antibodies 2
• The gastrointestinal symptoms may precede cancer diagnosis by months to years 2

Critical Diagnostic Algorithm

Initial Screening Tests (Beyond TSH)

1. Complete blood count, metabolic panel including calcium and glucose 2
2. Anti-tissue transglutaminase for celiac disease 2
3. Autoimmune panel: ANA, anti-centromere, anti-Scl70, anti-M3R for connective tissue disease 2
4. Chest imaging (X-ray or CT) to exclude thymoma or lung malignancy 2

Second-Tier Testing if Initial Screen Negative

1. Paraneoplastic antibody panel: ANNA-1, anti-CRMP-5, ganglionic AChR, anti-VGKC 2
2. Mitochondrial screening: plasma/urine thymidine and deoxyuridine, WBC thymine phosphorylase 2
3. Consider autonomic function testing if diabetic neuropathy suspected 2

Important Clinical Pitfalls

• Do not assume constipation is solely due to hypothyroidism if it preceded thyroid dysfunction or persists despite adequate thyroid replacement 4, 5
• The presence of amlodipine (a calcium channel blocker) can independently cause constipation, but this does not exclude concurrent systemic disease 2
• Autoimmune conditions can present sequentially over decades, so negative initial screening does not permanently exclude these diagnoses 3
• Mitochondrial disorders are relatively common (19% in one series of chronic intestinal pseudo-obstruction) but often missed 2
• Constipation severity disproportionate to thyroid dysfunction severity should prompt investigation for alternative or additional diagnoses 5, 6