Neoplasms of the Endocrine System

Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytomas are frequently familial and associated with genetic syndromes. Approximately 90% of pheochromocytomas are benign and surgical resection is the only curative treatment. Prognosis is generally good for benign, sporadic tumors that have been completely resected. Familial forms are associated with higher recurrence rates and malignant potential.

A gastrinoma is a tumor that secretes excessive levels of the hormone gastrin and is responsible for Zollinger-Ellison syndrome (ZES). Gastrinomas are frequently associated with multiple endocrine neoplasia 1 (MEN 1) and can arise from the pancreas, stomach, duodenum, jejunum, and/or even from the lymph nodes. Gastrinoma tumors are often malignant and frequently metastasize to the liver, lymph nodes, and bone. Zollinger-Ellison syndrome (ZES) is characterized by high gastrin levels, elevated gastric acid production, peptic ulcers, gastroesophageal reflux, and diarrhea. Diagnosis is based on fasting serum gastrin levels. Management consists of surgical resection of the gastrinoma and/or symptomatic management for unresectable disease.

A VIPoma is a rare neuroendocrine tumor arising primarily in the pancreas that releases large amounts of vasoactive intestinal polypeptide (VIP). This process leads to chronic watery diarrhea with concomitant hypokalemia and dehydration, as well as wheezing and flushing (known as Verner-Morrison or WDHA (chronic Watery Diarrhea, Hypokalemia, Achlorhydria) syndrome). Most tumors arise sporadically, but some are associated with MEN 1. Diagnosis is established by measuring serum VIP levels. Treatment consists of medical management of symptoms and complete surgical removal of the tumor when possible.

A glucagonoma is a glucagon-secreting neuroendocrine tumor that originates from the α-cells in the pancreatic islets. Most glucagonomas are malignant, and many of them are part of the autosomal dominant condition known as multiple endocrine neoplasia syndrome type 1 (MEN 1). Elevated levels of glucagon lead to increased gluconeogenesis and glycogenolysis, resulting in an increase in free glucose in the bloodstream and the depletion of fat and amino acid stores. Patients often present with diabetes, a characteristic rash called necrolytic migratory erythema, weight loss, anemia, deep vein thrombosis, and neuropsychiatric symptoms. Laboratory findings demonstrate an elevated glucagon level, and imaging shows a pancreatic mass. Management is usually supportive and includes glucagon inhibition with octreotide (a somatostatin analog). Surgical resection is attempted if disease is localized, though this is frequently palliative. Chemotherapy and targeted molecular agents are also used in advanced disease.

A thyroid nodule is a disordered growth of thyroid cells that produces a mass in the thyroid gland. Most thyroid nodules are benign and detected either by the patient or by the clinician on examination. In other cases, a thyroid nodule is found in radiologic imaging incidentally. Ruling out of malignancy is important. Workup includes thyroid-stimulating hormone (TSH) and thyroid ultrasound followed by radioactive iodine (RAI) uptake scan or thyroid scan if initial tests suggest the presence of hyperthyroidism. Fine-needle aspiration biopsy (FNAB) is recommended in patients with suspicious ultrasound findings, "cold" nodules (iodine uptake < surrounding tissue) on thyroid scan, large nodules (generally > 1.5 cm), or risk factors for malignancy. Management is dictated by pathology findings and can range from periodic ultrasound monitoring to surgery.

Neuroblastoma is a malignancy that arises from the neural crest cell derivatives along the sympathetic chain (neuroblasts) and is most commonly located in the adrenal medulla. The tumor often presents in childhood with a flank mass that crosses the midline. Neuroblastoma can also manifest as opsoclonus-myoclonus paraneoplastic syndrome. The tumor is diagnosed through biopsy, and supporting data include measuring the catecholamine breakdown products such as vanilmandelic acid (VMA) and homovanillic acid (HVA) in urine. Imaging studies are needed to localize the tumor. Management depends on several factors such as the stage of malignancy and the patient’s age at the time of diagnosis. Prognosis is favorable in the early stages of neuroblastoma.

Gastric acid medications include proton pump inhibitors (PPIs) and H₂ receptor antagonists (also known as H₂ blockers). The drugs work through different mechanisms to suppress acid secretion by parietal cells in the stomach. The most common indications include peptic ulcer disease, GERD, and dyspepsia. Adverse effects of PPIs include malabsorption, acute interstitial nephritis, and an increased risk of Clostridioides difficile infection. Adverse effects of H₂ blockers include CNS effects, bradycardia/hypotension, gynecomastia, and galactorrhea. Both classes are associated with drug interactions related to the cytochrome P450 system.

The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck, spanning the regions between the C5 and T1 vertebrae and encircling the anterolateral trachea. The left and right lobes of the thyroid gland are connected by a central isthmus. Important processes in metabolism, growth, cardiac function, and calcium homeostasis are regulated by the thyroid hormones (thyroxine and triiodothyronine) and calcitonin.

Sturge-Weber syndrome (SWS) is a congenital neurocutaneous disorder presenting with a facial birthmark called a port-wine stain (PWS), neurological abnormalities such as seizures, and eye abnormalities such as glaucoma. Not all of these symptoms have to be present in an affected individual, and some may develop later in life. While the condition is congenital, it is not inherited, as the causative mutation in the gene GNAQ is somatic and sporadic. Diagnosis is suspected based on symptoms and neuroimaging and confirmed with genetic testing. Management is targeted at symptom management and prevention of seizures and hemiparesis.

Von Hippel-Lindau (VHL) disease is an autosomal dominant genetic condition resulting from a deletion or mutation in the VHL gene. Individuals diagnosed with VHL disease have tumors and cysts in various parts of their bodies and may present with hemangioblastomas, renal cell carcinoma (RCC), pheochromocytoma, endolymphatic sac tumors of the middle ear, pancreatic tumors, and papillary cystadenomas of the epididymis or the broad ligament. The diagnosis is by genetic testing, laboratory evaluation of BUN, laboratory evaluation for the presence of catecholamines in the blood or urine, fundoscopic exam of the eye to detect hemangioblastoma of the retina, and CT/MRI to detect any other tumors. Management of the disease includes surgical removal of tumors.

Thyroid cancer is a malignancy arising from the thyroid gland cells: thyroid follicular cells (papillary, follicular, and anaplastic carcinomas) and calcitonin-producing C cells (medullary carcinomas). Rare cancers are derived from the lymphocytes (lymphoma) and/or stromal and vascular elements (sarcoma). Driver mutations involving the receptor tyrosine kinase pathway (such as RET and BRAF) and a family history of cancer or related syndromes increase the risk. Exposure to ionizing radiation and iodine deficiency are also considered risk factors. The major types can present as thyroid nodules or enlarged cervical lymph nodes. The diagnostic approach includes thyroid-stimulating hormone, ultrasonography, and biopsy. Treatment options are surgical removal of the thyroid gland, with the addition of radioactive iodine therapy and systemic therapy, depending on the type and extent of the thyroid malignancy.

Multiple endocrine neoplasia syndromes are autosomal dominant inherited conditions characterized by 2 or more hormone-producing tumors involving the endocrine organs. There are different types of MEN, namely MEN1–4. The MEN1 syndrome is associated with MEN1 gene mutation and has a predilection for primary hyperparathyroidism, pituitary adenomas, and pancreatic tumors (the 3 P’s). Due to the RET proto-oncogene mutation, MEN2 syndrome can be further categorized as MEN2A and MEN2B. Medullary thyroid carcinoma and pheochromocytoma are common features. The MEN2A variant is associated with primary hyperparathyroidism, whereas MEN2B (also considered MEN3) is associated with neuromas and Marfanoid habitus. The newer and rare entity, MEN4, has features of MEN1 but results from CDKN1B mutations. The diagnosis is clinical, and tumors are detected based on imaging and correlating hormone levels. Genetic testing plays a crucial role in MEN2 syndromes in determining further management. Treatment is dependent on the tumors that are present and genetic mutation.

A goiter is a chronic enlargement of the thyroid gland due to nonneoplastic growth occurring in the setting of hypothyroidism, hyperthyroidism, or euthyroidism. Morphologically, thyroid enlargement can be diffuse (smooth consistency) or nodular (uninodular or multinodular). Hashimoto’s thyroiditis is associated with a benign hypothyroid goiter, while Graves’ disease produces a toxic or hyperthyroid goiter. Nontoxic goiter is euthyroid and is usually due to iodine deficiency (the most common cause of goiter). Diagnostic tests include thyroid function tests and measurement of thyroid antibodies. Ultrasound, CT, and/or MRI help if lab results are ambiguous and if worrisome features such as obstructive symptoms are present. Radioactive iodine uptake distinguishes hyperthyroid causes. Treatment depends on the underlying condition; options include observation, medication, surgery, and radioiodine ablation.

Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytomas are frequently familial and associated with genetic syndromes. Approximately 90% of pheochromocytomas are benign and surgical resection is the only curative treatment. Prognosis is generally good for benign, sporadic tumors that have been completely resected. Familial forms are associated with higher recurrence rates and malignant potential.