Endocrine Disorders - Gastrointestinal Manifestations

Overview

Thyroid hormone status influences GI anatomy, motility, secretion, and immune interactions. Both hypothyroidism and hyperthyroidism produce multisystem GI effects that range from mild symptoms to life‑threatening complications. Treating the underlying thyroid disorder often reverses many GI abnormalities; coordination with pediatric endocrinology is essential.

Hypothyroidism — GI manifestations and mechanisms

Typical GI complaints

• Constipation (most common), often progressive and resistant to standard laxatives
• Anorexia, early satiety, nausea, vomiting, abdominal pain, bloating
• Failure to thrive in infants/young children with prolonged disease

Esophageal dysfunction

• Decreased lower esophageal sphincter pressure and reduced esophageal peristaltic amplitude → dysphagia and predisposition to gastroesophageal reflux disease (GERD)
• Goiter can produce external compression of the esophagus causing mechanical dysphagia and aspiration risk

Gastric dysfunction

• Delayed gastric emptying from smooth muscle hypocontractility, antral–duodenal discoordination, and pylorospasm
• Phytobezoar formation may occur and can cause gastric outlet obstruction
• Autoimmune gastritis with antiparietal cell antibodies may produce hypochlorhydria and pernicious anemia, contributing to malabsorption

Small intestinal effects

• Small intestinal hypomotility favors stasis and predisposes to small intestinal bacterial overgrowth (SIBO) with bloating, flatulence, and abdominal discomfort
• Malabsorption can follow; consider SIBO testing if symptoms persist despite thyroid replacement

Colonic dysfunction

• Colonic hypomotility can lead to obstipation, ileus, megacolon, or volvulus in severe cases
• Bowel distension may compromise mucosal perfusion and produce ischemia when extreme
• Megacolon and pseudovolvulus are rare and usually associated with severe hypothyroidism or myxedema coma; these often respond to thyroid hormone replacement
• Radiographic findings (distended loops, thickened haustrations) may mimic mechanical obstruction; differentiate clinically
• Surgery is at higher risk of prolonged postoperative ileus in hypothyroid patients

Other findings

• Ascites with high protein (>2.5 g/dL), variable SAAG, lymphocyte predominance — typically resolves with thyroid replacement rather than diuretics
• Autoimmune comorbidity (celiac disease, autoimmune gastritis/pernicious anemia, type 1 diabetes, inflammatory bowel disease) may coexist — consider targeted testing when indicated

Hyperthyroidism — GI manifestations and mechanisms

Typical GI complaints

• Abdominal pain, nausea, vomiting
• Weight loss despite normal or increased appetite; failure to thrive in children with chronic disease
• Frequent stools or overt diarrhea

Esophageal dysfunction

• Dysphagia due to goiter mass effect or thyrotoxic skeletal myopathy; manometry may show increased contraction velocity
• Consider imaging when mechanical compression is suspected

Gastric dysfunction

• Gastric emptying can be normal, rapid, or delayed depending on patient and disease factors
• Up to one‑third of patients may have decreased gastric acid secretion from antiparietal cell antibodies
• Hypergastrinemia may be present as a response to low acid or β‑adrenergic receptor mechanisms

Small intestinal effects

• Diarrhea is multifactorial: accelerated orocecal transit, altered pancreatic exocrine function (relative trypsinogen effects), and increased bile acid secretion can all contribute
• Diarrhea often improves with β‑blockade (e.g., propranolol) and definitive antithyroid therapy

Colon and motility

• Increased stool frequency is common; severe colonic complications are rare
• Hyperthyroidism may exacerbate preexisting motility disorders

Other metabolic effects

• Weight loss, negative nitrogen balance, and muscle wasting from increased basal metabolic rate and catabolism

Diagnostic approach for gastroenterologists

When to suspect thyroid contribution

• New or worsening severe constipation, ileus, or pseudo‑obstruction without clear surgical cause
• Unexplained chronic diarrhea with concurrent thyroid symptoms or signs (palpitations, heat intolerance, goiter, tachycardia)
• Dysphagia in the presence of goiter or unexplained motility abnormalities
• Unexplained nutrient deficiencies or autoimmune comorbidity

Initial tests to order

• Thyroid‑stimulating hormone (TSH) and free thyroxine (free T4) as first‑line screening
• Thyroid autoantibodies when autoimmune thyroid disease suspected (TPO, thyroglobulin antibodies)
• Antiparietal cell and intrinsic factor antibodies and serum B12 if pernicious anemia suspected
• Basic metabolic panel, albumin, liver tests, and inflammatory markers as clinically indicated
• Motility and malabsorption testing as needed: gastric emptying study, breath testing or jejunal aspirate for SIBO, fecal fat, celiac serologies, and abdominal imaging for obstruction
• Endoscopy with biopsies when mucosal disease, ulcers, or GI bleeding present

Management principles and coordination with endocrinology

Hypothyroidism

• Levothyroxine replacement is the cornerstone and often reverses motility and secretory abnormalities
• Supportive GI measures while repletion occurs:
  • Bowel regimens for constipation (osmotic and stimulant laxatives as appropriate)
  • Endoscopic or surgical removal of bezoars when obstructive
  • Replace deficient nutrients (B12, fat‑soluble vitamins, iron)
  • Consider testing and targeted treatment for SIBO if symptoms persist
• Severe myxedema ileus requires urgent IV thyroid hormone, critical care, and GI supportive care

Hyperthyroidism

• Definitive management per endocrinology: antithyroid drugs, β‑blockade (for symptomatic control and diarrhea improvement), radioactive iodine when appropriate, or surgery
• Symptomatic GI care: antidiarrheals when safe, bile acid sequestrants for bile acid diarrhea, pancreatic enzyme replacement when exocrine insufficiency documented
• Reassess GI symptoms after euthyroid state achieved

Perioperative and procedural considerations

• Optimize thyroid status preoperatively when feasible: hypothyroid patients have higher risk of prolonged ileus and delayed wound healing; hyperthyroid patients risk thyroid storm during stress
• Coordinate perioperative endocrine planning for moderate/severe thyroid disease

Red flags and urgent issues for gastroenterologists

• Myxedema coma or severe hypothyroidism with ileus, hypothermia, bradycardia, or hypotension — emergency endocrine and critical care management required
• Severe dehydration, electrolyte disturbances, or hemodynamic instability from thyrotoxicosis‑related diarrhea — urgent stabilization and endocrine coordination
• Progressive dysphagia with airway compromise from large goiter — urgent ENT/endocrine/surgical referral
• Recurrent unexplained malabsorption or severe nutrient deficiency despite therapy — evaluate for autoimmune gastritis, SIBO, or celiac disease

Key takeaways for pediatric gastroenterology practice

• Include basic thyroid testing (TSH ± free T4) in the workup of unexplained severe motility disorders, new refractory diarrhea, dysphagia with goiter, or unexplained malabsorption
• Many GI manifestations are reversible with restoration of euthyroidism, but supportive and sometimes interventional GI care is often needed while endocrine therapy takes effect
• Coordinate care early with pediatric endocrinology, nutrition, and surgery for severe or complicated cases
• Be vigilant for autoimmune comorbidities (celiac disease, type 1 diabetes, autoimmune gastritis) and test when the clinical context suggests overlap

Cushing Syndrome

Cushing syndrome

• Complications from glucocorticoid excess: central/generalized obesity, failure of longitudinal growth, hirsutism, proximal muscle weakness, nuchal (buffalo hump) fat pad, acne, purple striae, and hypertension
• Gastric/duodenal ulcers are more likely in patients receiving chronic steroid therapy
• Patients may develop secondary GI complications of diabetes mellitus (e.g., gastroparesis, nonalcoholic fatty liver disease) associated with hypercortisolemia

Addrenal Insufficiency

Adrenal insufficiency (Addison disease)

A. Gastric dysfunction

• GI symptoms common: >50% report anorexia, weight loss, nausea, vomiting, diarrhea, and abdominal pain
• Presentation can mimic cyclic vomiting syndrome with episodic severe vomiting
• Associated with atrophic gastritis, achlorhydria, and pernicious anemia in autoimmune Addison disease

B. Small bowel dysfunction

• Malabsorption, chronic diarrhea, and failure to thrive may result from functional enterocyte defects and generally improve with glucocorticoid replacement
• Associated celiac disease described in 8%–12% of patients; both conditions share HLA associations and may coexist

C. Liver dysfunction

• Chronic mild elevation of aminotransferases may be seen in some patients with adrenal insufficiency

Pheochromocytoma

Pheochromocytoma

• GI manifestations: nausea, vomiting, abdominal pain; less commonly constipation, ileus, megacolon, ischemic colitis, and perforation
• Megacolon has been reported with large catecholamine‑secreting tumors
• GI effects due to excessive catecholamines can often be relieved by α‑adrenergic blockade (e.g., phentolamine) as part of preoperative medical management

Diagnostic considerations and coordination

When to suspect endocrine causes for GI symptoms

• Unexplained severe constipation, pseudo‑obstruction, or ileus
• Chronic unexplained diarrhea with systemic features (weight loss, tachycardia, heat intolerance, hypertension)
• Multisystem findings suggestive of Cushingoid features, adrenal insufficiency (fatigue, hyperpigmentation, hypotension), or catecholamine excess (paroxysmal hypertension, headaches)

Initial and targeted tests

• Basic endocrine screening targeted to clinical suspicion: TSH/free T4 for thyroid; morning cortisol/ACTH and adrenal stimulation testing for adrenal insufficiency; dexamethasone suppression and late‑night salivary cortisol for Cushing; plasma‑free metanephrines or 24‑hour urine metanephrines for pheochromocytoma
• Supportive GI testing as indicated: gastric emptying studies, breath tests for SIBO, fecal fat, celiac serologies, abdominal imaging for obstruction or mass
• Coordinate urgent endocrine consultation for suspected adrenal crisis, myxedema coma, thyroid storm, or pheochromocytoma preoperative preparation

Management principles

General

• Treat underlying endocrine disorder in coordination with pediatric endocrinology; many GI manifestations improve or resolve with correction of hormonal imbalance
• Supportive GI care (nutritional support, symptomatic therapies, endoscopic/surgical interventions) while endocrine therapies take effect
• Address comorbid autoimmune diseases that may require simultaneous workup and therapy

Urgent scenarios

• Adrenal crisis/Addisonian emergencies require immediate IV glucocorticoids, fluid resuscitation, and electrolyte correction
• Severe Cushing‑related complications (bleeding peptic ulcer, uncontrolled hyperglycemia) need combined medical and surgical/endoscopy management
• Pheochromocytoma patients require careful α‑blockade before surgery to reduce perioperative GI ischemic complications

Red flags and referral triggers

• Signs of adrenal crisis, myxedema coma, or thyroid storm — emergency endocrine and critical care management
• Unexplained GI bleeding or severe ulcers on steroids — urgent gastroenterology and endocrine input
• Recurrent severe malabsorption or failure to thrive despite standard therapy — consider endocrine causes and multidisciplinary evaluation

Hypoparathyroidism

Small bowel dysfunction

• Steatorrhea and malabsorption may be an early manifestation.
• Mechanism: hypocalcemia → reduced cholecystokinin (CCK) release → decreased gallbladder contraction and pancreatic enzyme secretion, impairing fat digestion.
• Diarrhea often normalizes with correction of hypocalcemia and adequate vitamin D therapy.
• Exclude magnesium deficiency, which can present with malabsorption and functional hypoparathyroidism and blunt response to calcium therapy.
• Occasionally associated with celiac disease; malabsorption may improve on a gluten‑free diet. Suspect celiac disease in hypoparathyroid patients whose serum calcium does not respond to treatment.

Hyperparathyroidism

General GI features

• Often due to sporadic parathyroid adenoma or as part of multiple endocrine neoplasia (MEN) syndromes.
• Hypercalcemia effects on gut and pancreas produce multiple GI manifestations.

Specific manifestations

• Gastroparesis from hypercalcemia‑related reduction in neuromuscular excitability → nausea, vomiting, and abdominal pain.
• Peptic ulcer disease related to increased gastric acid secretion in some patients.
• Reduced colonic transit → constipation.
• Acute pancreatitis occurs in a minority (~1.5%) of patients with primary hyperparathyroidism.

Acromegaly

Gastrointestinal effects

• Associated with increased colon length and circumference and reduced colonic transit time.
• Elevated risk of colonic polyps and colorectal cancer; heightened surveillance for colorectal neoplasia is recommended in adults and considered case‑by‑case in adolescents with acromegaly.
• Octreotide therapy can increase gallstone formation, likely via suppression of CCK release and impaired gallbladder emptying.

Diabetes Mellitus (DM)

Pathogenetic factors for GI symptoms

• Gastroparesis, altered intestinal motility, sphincter dysfunction, infection risk, and coexistence of autoimmune disorders (e.g., celiac disease, autoimmune atrophic gastritis).

Gestational diabetes

• Increased risk of pregnancy complications (spontaneous abortion, macrosomia, organomegaly, intrauterine growth restriction, neonatal hypoglycemia, jaundice, cardiomyopathy).
• Neonatal small left colon syndrome can produce postnatal obstructive symptoms.

Esophageal dysfunction

• Relatively uncommon but may include ↓ LES pressure, ↓ transit, and ↓ amplitude of contractions → esophageal dysmotility and increased GERD risk.
• Esophageal candidiasis may occur (odynophagia/dysphagia) particularly in immunocompromised or poorly controlled patients.

Gastroparesis

• Less common in children than adults but reported; related to antral dysrhythmia, abnormal gastroduodenal pressure dynamics, and pyloric dysfunction, often exacerbated by hyperglycemia.
• Symptoms: postprandial epigastric discomfort, bloating, nausea, vomiting, early satiety, and weight loss.
• Medications that worsen gastroparesis include anticholinergics, tricyclic antidepressants, benzodiazepines, and ganglionic‑blocking agents.
• Management: optimize glycemic control; antiemetics; low‑dose TCAs for visceral hypersensitivity; promotility agents (metoclopramide, domperidone where available, erythromycin); consider ghrelin agonists or gastric pacing for refractory cases.

Acute erosive gastritis

• May occur in the setting of diabetic ketoacidosis (DKA).

Autoimmune gastric disease

• 15%–20% of type 1 diabetes patients have antiparietal cell antibodies, autoimmune atrophic gastritis, pernicious anemia, iron deficiency, hypochlorhydria, and hypergastrinemia.

Small bowel dysfunction

• Celiac disease reported in up to 5%–10% of patients with type 1 diabetes; many are asymptomatic — consider screening per guidelines.
• Diarrhea etiologies: medications (metformin, α‑glucosidase inhibitors like acarbose/miglitol), coexistent celiac disease, pancreatic insufficiency, SIBO, autonomic neuropathy, insulinoma/islet cell tumor, or fecal incontinence related to neuropathy.
• Diarrhea tends to be worse in poorly controlled diabetes with autonomic neuropathy (DAN).

Colonic dysfunction

• Incontinence often occurs in the setting of diabetic diarrhea; steatorrhea reported in up to 30% in some series.
• Autonomic dysfunction impairs internal anal sphincter resting tone and reflex relaxation.
• Constipation related to DAN may be complicated by megacolon, pseudo‑obstruction, stercoral ulcer, perforation, volvulus, or overflow diarrhea.

Biliary tree and liver

• Increased risk of cholelithiasis, cholecystitis, and ascending cholangitis.
• Mild to moderate elevations in transaminases are common; nonalcoholic fatty liver disease (NAFLD) prevalence is increased.
• Rare hepatotoxicity reported with some antidiabetic agents (e.g., thiazolidinediones) and cholestatic reactions with sulfonylureas; monitor when clinically indicated.
• Mauriac syndrome (in children with poorly controlled diabetes): hepatomegaly with glycogen deposition, hypoglycemia, growth impairment, and Cushingoid features.

Pancreas

• Higher prevalence of acute pancreatitis and exocrine pancreatic insufficiency in diabetes.
• New‑onset diabetes may, rarely, be the first sign of pancreatic neoplasm and warrant evaluation when clinical suspicion exists.