A de novo heterozygous CASR mutation that is responsible for NHPT may also present in individuals with asymptomatic hypocalciuric hypercalcemia. [edmcasereports.com]

In addition, a 22-year-old man presented with hypercalcemia, fatigue, and generalized rib pain, and a 52-year-old woman who had an approximately 20-year history of hypercalcemia presented with headaches, abdominal pain, vomiting, fatigue, and musculoskeletal [nejm.org]

Presentation on theme: "Familial Hypocalciuric Hypercalcemia(FHH) CASR Disorders"— Presentation transcript: 1 Familial Hypocalciuric Hypercalcemia(FHH) CASR Disorders Gita Majdi, M.D, MRCP (UK), FRCPC,ABIM PGY5 Endocrinology Feb 2015 2 Objectives: Introduction [slideplayer.com]

Last updated May 3, 2018 Autosomal Dominant Hypocalcemia (ADH) is a genetic disorder that is inherited in an autosomal dominant manner, where one defective copy of either affected gene can cause the disorder if present in all the cells. [dovemed.com]

Disorders of the parathyroid glands most commonly present with abnormalities of serum calcium. [aafp.org]

• Weakness

  The symptoms frequently come on slowly and are usually subtle, such as a feeling of weakness or fatigue, or aches and pains. [healthguidance.org]

  HHC is usually asymptomatic but in some cases: fatigue, weakness, excessive thirst and concentration problems have been reported. Some adults present also pancreatitis, chondrocalcinosis and premature vascular calcification. [iofbonehealth.org]

  Affected individuals may also have fatigue, weakness, mental disturbance, and polydipsia/polyuria. [genedx.com]

  FHH is usually asymptomatic but rarely symptoms of fatigue, weakness, excessive thirst and concentration problems are experienced. Some adults suffer from relapsing pancreatitis, chondrocalcinosis and premature vascular calcification. [orpha.net]

• Falling

  The data clearly shows that patients with primary hyperparathyroidism don't naturally fall with a nice grouping above the number 100. They fall with a nice grouping from way down around 20 to way up to 1000 (as seen in the first graph). [parathyroid.com]

  Serum calcium begins to decrease in 2 to 4 h and falls to near-normal within 24 h. [merckmanuals.com]

  The post-operative PTH level should fall by >50% into the normal range. In patients who do not meet any criteria for surgery, a conservative, non-surgical approach is acceptable. [endocrinologyadvisor.com]

  Conversely, when the serum calcium concentration falls, parathyroid hormone secretion is stimulated, resulting in an increase in serum calcium. 23 24 CaRS The calcium-sensing receptor is a G-protein–coupled receptor that is highly expressed in parathyroid [slideplayer.com]

  This falls outside of the “minimally invasive” algorithm. We only perform an ultrasound of the neck, mainly to look for thyroid gland pathology that may need to be addressed. [entokey.com]

• Anemia

  P74 ) Endocrine, nutritional and metabolic diseases E70-E88 2019 ICD-10-CM Range E70-E88 Metabolic disorders Type 1 Excludes androgen insensitivity syndrome ( E34.5- ) congenital adrenal hyperplasia ( E25.0 ) Ehlers-Danlos syndrome ( Q79.6 ) hemolytic anemias [icd10data.com]

  Research indicates that PHPT may be associated with other disorders like multiple endocrine neoplasia, obesity, type 2 diabetes, anemia and monoclonal gammopathy, although some studies are conflicting for some disorders. [scorgloballifeamericas.com]

  Multiple myeloma is suggested by simultaneous anemia, azotemia, and hypercalcemia or by the presence of a monoclonal gammopathy. Myeloma is confirmed by bone marrow examination. [merckmanuals.com]

• Congestive Heart Failure

  […] sound Congestive heart failure or systolic or diastolic dysfunction from hypo- or hypercalcemia Dermatologic Dry, puffy skin Hypocalcemia Dry, brittle hair Hypocalcemia Candidiasis Polyglandular autoimmune syndrome with hypoparathyroidism Neuromuscular [aafp.org]

• Amyloidosis

  Erythrokeratodermie GJB4, LOR Erythromelalgie SCN9A Escobar syndrome, Multiple pterygium syndrome, lethal type CHRNG Exudative vitreoretinopathy FZD4, NDP, TSPAN12 Facio-scapulo-humerale Dystrophie FSHD Factor XIII deficiency F13A1, F13B Familial Transthyretin Amyloidosis [meduniwien.ac.at]

• Dyspnea

  Symptoms Associated with Hypercalcemia Organ system Most common symptoms and possible diagnoses Cardiovascular Angina, dyspnea, palpitations, syncope Possible diagnoses: diastolic dysfunction, dysrhythmias, hypertension, left ventricular hypertrophy, [aafp.org]

• Hypertension

  Wirth A et al. (2008) G12-G13-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension. [^] 6. Jiang M et al. (1991) Guanine nucleotide-binding regulatory proteins in retinal pigment epithelial cells. [^] 7. [moldiag.com]

  She had also sometimes exhibited slight elevation of parathyroid hormone (97 pg/ml) while receiving treatment for hypertension and heart failure with atrial fibrillation, which had been detected by the Department of Cardiology at 71 years of age. [jlc.jst.go.jp]

  Symptoms Associated with Hypercalcemia Organ system Most common symptoms and possible diagnoses Cardiovascular Angina, dyspnea, palpitations, syncope Possible diagnoses: diastolic dysfunction, dysrhythmias, hypertension, left ventricular hypertrophy, [aafp.org]

  Still, concerns about hypertension and longevity remain. [merckmanuals.com]

  Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities. Nature 482, 98–102 (2012). 33. Lunter, G. & Goodson, M. Stampy: a statistical algorithm for sensitive and fast mapping of Illumina sequence reads. [nature.com]

• Heart Failure

  Failure and Transplantation Cardiology Nita Ahuja MD, MBA Gastrointestinal Surgical Oncology, General Surgery, Minimally Invasive Surgery, Sarcoma and Connective Tissue Surgical Oncology Paul Aiello MD Radiology, Diagnostic Radiology Joseph Akar MD, [yalemedicine.org]

  She had also sometimes exhibited slight elevation of parathyroid hormone (97 pg/ml) while receiving treatment for hypertension and heart failure with atrial fibrillation, which had been detected by the Department of Cardiology at 71 years of age. [jlc.jst.go.jp]

  […] sound Congestive heart failure or systolic or diastolic dysfunction from hypo- or hypercalcemia Dermatologic Dry, puffy skin Hypocalcemia Dry, brittle hair Hypocalcemia Candidiasis Polyglandular autoimmune syndrome with hypoparathyroidism Neuromuscular [aafp.org]

  Initially, 1 to 2 L of saline is given over 2 to 4 h unless significant heart failure is present because nearly all patients with significant hypercalcemia are hypovolemic. [merckmanuals.com]

• Brittle Hair

  hair Hypocalcemia Candidiasis Polyglandular autoimmune syndrome with hypoparathyroidism Neuromuscular Chvostek sign Hypocalcemia Trousseau sign Hypocalcemia Emotional instability, anxiety, depression Hypo- or hypercalcemia Cognitive dysfunction, dementia [aafp.org]

[…] severe primary hyperparathyroidism Establishing a diagnosis of autosomal dominant hypoparathyroidism As part of the workup of idiopathic hypoparathyroidism As part of the workup of patients with Bartter syndrome Clinical Information Discusses physiology [mayomedicallaboratories.com]

Genetic testing is an important part of the workup in the assessment of patients with suspected MEN 2 syndrome, and the clinical features and tumor behavior are closely related to the specific RET germ-line mutation present. [entokey.com]

Make the best clinical decisions with an enhanced emphasis on evidence-based practice and expert opinions on treatment strategies. Zero in on the most relevant and useful references with the aid of a more focused, concise bibliography. [books.google.com]

Relating to Osteoporosis Lstrand: Are there any new treatments for osteoporosis? Leila_Khan,_MD: There are several new treatments coming in the next few months. Stay tuned! [my.clevelandclinic.org]

A fall of 50% or more 10 min after removal of the adenoma indicates successful treatment. [merckmanuals.com]

The cost of cinacalcet (Sensipar) ranges from $4,000 to $23,500 per year, depending on the dosage. 57 Treatment of CaSR Oral CaSR antagonists (calcilytics) are in development for the treatment of osteoporosis. [slideplayer.com]

You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments. [rarediseases.info.nih.gov]

(Outcomes/Resolutions) The prognosis of Autosomal Dominant Hypocalcemia is reported to be dictated by the type and severity of symptoms in the affected individuals Individuals with mild signs and symptoms of ADH have better prognosis than those with severe [dovemed.com]

Prognosis Familial hypocalciuric hypercalcemia is a benign disease. Complications Hypercalcemia can cause pancreatitis and chondrocalcinosis. Lipomas are frequent too. Bibliography Aida, K., Koishi, S., Inoue, M., Nakazato, M., Tawata, M., Onaya, T. [renaltube.com]

Prognosis FHH does not lower life expectancy and has a benign, stable course. The documents contained in this web site are presented for information purposes only. [orpha.net]

Quite often, hypercalcemia is a late finding in malignancy, and it often portends a poor prognosis. If the PTHrP is not elevated, physicians turn to the Vitamin D levels in the evaluation of hypercalcemia. [scorgloballifeamericas.com]

Review Summary Nature Reviews Nephrology 2008年2月1日 Hereditary etiologies of hypomagnesemia PubMedおよびOvidデータベースを用いて文献検索を実施した。 [natureasia.com]

Etiology There are 3 genetic types of FHH based on chromosome location. FHH type 1 accounts for 65% of cases and is due to inactivating mutations in the CASR gene, localized to 3q21.1. This gene encodes the calcium-sensing receptor (CaSR). [orpha.net]

The etiology of MEN1 syndrome is menin inactivation. [hormones.gr]

Typically, diagnosis is made in the pursuit of uncovering the etiology of hypercalcemia. Calcium levels are often in the high normal range or slightly elevated. [en.wikipedia.org]

[…] type 1 Classification (Orphanet): - Rare bone disease - Rare developmental defect during embryogenesis - Rare endocrine disease - Rare genetic disease - Rare respiratory disease Classification (ICD10): - Endocrine, nutritional and metabolic diseases - Epidemiological [csbg.cnb.csic.es]

Summary Epidemiology Prevalence is unknown. [orpha.net]

Yu N et al. ”A record linkage study of outcomes in patients with mild primary hyperparathyroidism: The Parathyroid Epidemiology and Audit Research Study (PEARS).” Clinical Endocrinology, 2011 75:169–176. Alfadda TI et al. [scorgloballifeamericas.com]

"Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research". J. Bone Miner. Res. 26 (10): 2317–37. doi : 10.1002/jbmr.483. PMC 3405491. [wikidoc.org]

From basic science and pathophysiology to clinical best practices, Brenner & Rector’s The Kidney is your go-to resource for any stage of your career. [books.google.com]

[…] severe primary hyperparathyroidism Establishing a diagnosis of autosomal dominant hypoparathyroidism As part of the workup of idiopathic hypoparathyroidism As part of the workup of patients with Bartter syndrome Clinical Information Discusses physiology, pathophysiology [mayomedicallaboratories.com]

"Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research". J. Bone Miner. Res. 26 (10): 2317–37. doi : 10.1002/jbmr.483. PMC 3405491. [wikidoc.org]

Cotter, Hypothesis review: are clathrin-mediated endocytosis and clathrin-dependent membrane and protein trafficking core pathophysiological processes in schizophrenia and bipolar disorder? Mol. [link.springer.com]

[…] inappropriately normal or the frankly elevated parathyroid hormone levels in these conditions result from a defect in calcium sensing that affects all parathyroid tissue, subtotal parathyroidectomy does not usually lead to long-term normocalcemia. 8 9 10 Pathophysiology [slideplayer.com]

Kero J et al. (2007) Thyrocyte-specific Gq/G11 deficiency impairs thyroid function and prevents goiter development. [^] 5. [moldiag.com]

The mainstay for treatment in patients with MEN 2, with early identification of germ-line mutations in the RET gene, is prophylactic thyroidectomy to prevent medullary thyroid carcinoma. [entokey.com]

Measures used for treatment can also be used for prevention. One aim is to prevent hyperphosphatemia. Treatment combines dietary phosphate restriction and phosphate binding agents, such as calcium carbonate or sevelamer. [merckmanuals.com]

Center for Research, Prevention and Treatment of Atherosclerosis Hadassah-Hebrew University Medical Center Jerusalem Israel 3. Pediatric Endocrinology, Armon Child Center Carmel Hospital, Clalit Health Service Haifa Israel 4. [link.springer.com]