Endocrine Disorders
Pancreatic Disease
Thyroid Disease
Sexual Hormones
Adrenal Disease
Pancreatic Disease
Autoimmune pancreatitis
Diabetes Mellitus
Hyperinsulinemic Hypoglycemia
Autoimmune pancreatitis
Definition:
Autoimmune pancreatitis is a rare systemic fibrotic inflammatory disorder that can affect the bile ducts, salivary glands, and retroperitoneal lymph nodes, in addition to the pancreas. Common symptoms of autoimmune pancreatitis include jaundice, weight loss, and mild abdominal pain (4, 5).
Panel test for Autoimmune pancreatitis
Initial testing
Liver functional tests: May show an obstructive pattern
Lipase: May be elevated, Nonspecific marker for pancreatic damage
CBC: Useful in evaluation for malignancy, does not provide information for diagnosis of AIP
Serum IgG4: ≥2-fold elevation of IgG4 highly suggestive of AIP
IgG4 elevated in ~66% of patients.
CA19-9: elevated in 50% of patients with AIP. Also elevated in pancreatic cancer, but not specific.
Diabetes Mellitus
Definition:
Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels.
Diabetes-Related Autoantibodies
Islet cell antibodies (ICAs): Islet autoantibodies are markers that appear when insulin producing beta cells in pancreas are damaged. They can be detected a long time before beta cells are completely destroyed.
Insulin antibodies (IAs): In addition to attacking beta cells, the immune system in people with type 1 diabetes also targets insulin. This test looks for the antibodies targeting insulin.
Glutamic acid decarboxylase antibodies (GADAs, or GAD 65): This test looks for antibodies built against a specific enzyme in the pancreatic beta cells that produce insulin.
Insulinoma-associated antigen 2: This test looks for antibodies mounted against a specific enzyme in beta cells. Both the IA-2A and GADA tests are common type 1 antibody tests performed at endocrinology offices.
Zinc transporter (ZnT8) antibodies: The newest type 1 test, this looks at antibodies targeting an enzyme that is specific to beta cells. This test may not be as readily available.
Comment:
Routine screening for Type 1 Diabetes Melitus (T1DM) risk with autoantibodies is recommended only in the setting of a research trial or in first-degree family members of a proband with T1DM.
Hyperinsulinemic Hypoglycemia
Definition:
Hyperinsulinemic hypoglycemia (HH) is biochemically characterized by the unregulated secretion of insulin from the pancreatic β-cells in the presence of low blood glucose levels. HH is a major cause of brain injury and mental retardation in children. Postprandial hyperinsulinemic hypoglycemia in adults can be cause by noninsulinoma pancreatogenous hypoglycemia syndrome, gastric bypass surgery for morbid obesity, or mutations in the insulin receptor gene(6, 7).
Insulin antibodies
Presence suggests administration of insulin, rather than endogenous insulin such as that secreted by insulinoma
Thyroid Disease
Autoimmune Thyroiditis
Definition:
Autoimmune thyroiditis is an inflammatory state of the thyroid gland that results from the interaction between genetic variants that promote susceptibility and environmental factors. Autoimmunity to thyroid antigens leads to two distinct pathogenic processes with opposing clinical outcomes: hypothyroidism in Hashimoto’s thyroiditis and hyperthyroidism in Graves’ disease.High iodine intake, selenium deficiency, pollutants such as tobacco smoke, infectious diseases such as chronic hepatitis C, and certain drugs are implicated in the development of autoimmune thyroiditis, primarily in genetically predisposed people(10, 11).
Panel test for autoimmune thyroiditis:
Thyroid stimulating hormone (TSH) followed by free T4 – establish presence of hypo- or hyperthyroidism
Hashimoto thyroiditis (HT): most likely if patient is hypothyroid: Elevated TSH and low free T4
Graves disease GD – most likely if patient is hyperthyroid: Low TSH and elevated free T4
Antibody screening: as a follow-up when thyroid disease identified
TPO Antibodies: TPO is a transmembrane protein essential for synthesis of thyroid hormones, TPO is targeted by the thyroid microsomal antibody. Polyclonal antibody (usually IgG1, IgG4). Present in >90% of individuals Presence of antibody is pathognomonic for HT.
TSH Receptor Antibodies (TRAb): TSH-specific receptor controls thyroid function and cell growth. TRAb targets TSH receptors and competes with TSH for receptor binding.
3 classes (IgG antibodies)
Stimulating antibodies – also known as LATS or thyroid-stimulating antibodies
Blocking antibodies – may be etiology of hypothyroidism
Neutral antibodies
This test measures both stimulating and blocking antibodies
Thyroglobulin Antibodies: Tg is the precursor to thyroid hormones and is highly immunoreactive. Tg antibody is directed against thyroglobulin. Present in 40-70% of individuals. Provides no additional information over TRAb or TPO antibodies. Present in 60-80% of individual presence of antibody is diagnostic, but provides no additional information over TPO antibodies.
Algorithm:
Sexual Hormones
Polycystic Ovarian Syndrome – PCOS
Definition:
Polycystic Ovarian Syndrome (PCOS) is one of the most common endocrine and metabolic disorders in premenopausal women.PCOS is defined by a combination of signs and symptoms of androgen excess and ovarian dysfunction in the absence of other specific diagnoses.
PCOS represents a condition in which an estimate of 10 small cysts of a diameter ranging between 2 and 9 mm develop on one or both ovaries and/or the ovarian volume in at least one ovary exceeds 10 ml (8, 9).
Anti-Mullerian hormone (AMH):
AMH is an excellent test for ovarian reserve, which correlates with egg quality/number. Measurement of follicle stimulating hormone (FSH) on the third day of a period has also been shown to be a good test of ovarian reserve. However, as women age through their mid 30s and early 40s, AMH is a much better ovarian reserve test.
AMH level is one measure of reproductive performance. Age is also very important.
Women with higher AMH levels typically respond better to ovarian stimulation during an in vitro fertilization (IVF) cycle. This is because women with a lower AMH level produce a lower number of eggs.
| AMH Reference Intervals for Females | |
| Age | Reference Interval (ng/mL) |
| 6 mos-14 yrs | 0.256-6.345 |
| 15-17 yrs | 0.861-10.451 |
| 18-29 yrs | 0.401-16.015 |
| 30-39 yrs | 0.176-11.705 |
| 40-45 yrs | ≤6.282 |
| 46-50 yrs | ≤0.064 |
| Postmenopausal | ≤0.003 |
Algorithm:
Adrenal Disease
Adrenal insufficiency
Definition:
Adrenal insufficiency is caused by failure of the adrenal cortex to produce cortisol. This failure can result from loss of function of the adrenal glands (primary adrenal insufficiency), which is most frequently caused by autoimmune adrenalitis (Addison’s disease) and inherited disruption of glucocorticoid synthesis by congenital adrenal hyperplasia. Secondary adrenal insufficiency is caused by impaired hypothalamic-pituitary regulation of synthesis of adrenal cortisol, mostly caused by tumors of the hypothalamic-pituitary region and their treatment with surgery or radiotherapy(2, 3).
Panel test for adrenal insufficiency
21-Hydroxylase Antibody
A positive 21-hydroxylase antibody test result confirms an autoimmune etiology of Primary adrenal insufficiency (PAI), in which the body’s own immune response attacks adrenal tissue. If the 21-hydroxylase test result is negative, other causes should be investigated.
Autoimmune polyglandular syndrome
Definition:
Autoimmune polyendocrinopathy type 1, or APECED syndrome, is a genetic disease that manifests in childhood or early adolescence with a combination of chronic mucocutaneous candidiasis, hypoparathyroidism and autoimmune adrenal failure.
Panel test for Autoimmune polyglandular syndrome:
Detects mutations (including point mutations, deletions, insertions, and rearrangements) in the coding sequences of AIRE.
Algorithm:
References:
Li M, Ge Q, Sheng C-s, Zhang J, Li H, Niu W, et al. Clinical characteristics of snoring patients with primary aldosteronism and obstructive sleep apnea–hypopnea syndrome. Journal of human hypertension. 2019.
Bancos I, Hahner S, Tomlinson J, Arlt W. Diagnosis and management of adrenal insufficiency. The lancet Diabetes & endocrinology. 2015;3(3):216-26.
Tomlinson JW, Holden N, Hills RK, Wheatley K, Clayton RN, Bates AS, et al. Association between premature mortality and hypopituitarism. West Midlands Prospective Hypopituitary Study Group. Lancet (London, England). 2001;357(9254):425-31.
Pickartz T, Mayerle J, Lerch MM. Autoimmune pancreatitis. Nature Clinical Practice Gastroenterology &Amp; Hepatology. 2007;4:314.
Fan B-G, Andrén-Sandberg A. Autoimmune pancreatitis. N Am J Med Sci. 2009;1(4):148-51.
Nessa A, Rahman SA, Hussain K. Hyperinsulinemic Hypoglycemia – The Molecular Mechanisms. Front Endocrinol (Lausanne). 2016;7:29-.
Kapoor RR, James C, Hussain K. Advances in the diagnosis and management of hyperinsulinemic hypoglycemia. Nature Clinical Practice Endocrinology &Amp; Metabolism. 2009;5:101.
El Hayek S, Bitar L, Hamdar LH, Mirza FG, Daoud G. Poly Cystic Ovarian Syndrome: An Updated Overview. Frontiers in physiology. 2016;7:124-.
Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nature Reviews Endocrinology. 2018;14:270.
Duntas LH. Environmental factors and autoimmune thyroiditis. Nature Clinical Practice Endocrinology &Amp; Metabolism. 2008;4:454.
Stassi G, De Maria R. Autoimmune thyroid disease: new models of cell death in autoimmunity. Nature Reviews Immunology. 2002;2(3):195-204.
