scholarly journals The Biochemical Profile of Familial Hypocalciuric Hypercalcemia and Primary Hyperparathyroidism during Pregnancy and Lactation: Two Case Reports and Review of the Literature

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
S. A. Ghaznavi ◽  
N. M. A. Saad ◽  
L. E. Donovan
Keyword(s):  
Primary Hyperparathyroidism ◽  
Case Reports ◽  
Diagnostic Error ◽  
Calcium Handling ◽  
Familial Hypocalciuric Hypercalcemia ◽  
Second Trimester ◽  
Clearance Ratio ◽  
Fetal Complications ◽  
Pregnancy And Lactation ◽  
History Of

Background. Primary hyperparathyroidism (PHPT) and Familial Hypocalciuric Hypercalcemia (FHH) result in different maternal and fetal complications in pregnancy. Calcium to creatinine clearance ratio (CCCR) is commonly used to help distinguish these two conditions. Physiological changes in calcium handling during pregnancy and lactation can alter CCCR, making it a less useful tool to distinguish PHPT from FHH. Cases. A 25-year-old female presented with hypercalcemia and an inappropriately normal PTH. Her CCCR was 0.79% before pregnancy and rose to 1.99% in her second trimester. The proband’s mother and neonate had asymptomatic hypercalcemia. Genetic analysis revealed a CaSR mutation consistent with FHH. A 19-year-old female presented with a history of nephrolithiasis who underwent emergent caesarean section at 29 weeks of gestation for severe preeclampsia. At delivery, she was diagnosed with hypercalcemia with an inappropriately normal PTH and a CCCR of 2.67%, which fell to 0.88% during lactation. Parathyroidectomy cured her hypercalcemia. Pathology confirmed a parathyroid adenoma. Conclusion. These cases illustrate the influence of pregnancy and lactation on renal calcium indices, such as the CCCR. To avoid diagnostic error of women with hypercalcemia during pregnancy and lactation, calcium biochemistry of first-degree relatives and genetic testing of select patients are recommended.

scholarly journals Familial Hypocalciuric Hypercalcemia in an Index Male: Grey Zones of the Differential Diagnosis From Primary Hyperparathyroidism in a 13-Year Clinical Follow up

2020 ◽  
pp. S321-S328
Author(s):  
K. ZAJÍČKOVÁ ◽  
M. DVOŘÁKOVÁ ◽  
J. MORAVCOVÁ ◽  
J. VČELÁK ◽  
D. GOLTZMAN
Keyword(s):  
Differential Diagnosis ◽  
Family History ◽  
Primary Hyperparathyroidism ◽  
Familial Hypocalciuric Hypercalcemia ◽  
Clearance Ratio ◽  
Japanese Family ◽  
Casr Gene ◽  
History Of ◽  
Inactivating Mutation

Familial hypocalciuric hypercalcemia (FHH) type 1, caused by a heterozygous inactivating mutation of the gene encoding the calcium-sensing receptor (CaSR), is characterized by mild to moderate hypercalcemia, hypocalciuria and inappropriately normal or elevated parathyroid hormone (PTH). FHH must be differentiated from primary hyperparathyroidism (PHPT) because parathyroidectomy is ineffective in the former. Herein, we report a 39-year-old male patient with a 13-year history of asymptomatic PTH-dependent hypercalcemia (mean calcium of 2.88 mmol/l; reference range 2.15-2.55 mmol/l) and calcium-to-creatinine clearance ratio (Ca/Cr) ranging from 0.007 to 0.0198, which is consistent with either FHH or PHPT. Although a family history of hypercalcemia was negative, and PET-CT with fluorocholine was suggestive of a parathyroid adenoma, genetic analysis of the CaSR gene identified a heterozygous inactivating mutation NM_000388.4:c.1670G>A p. (Gly557Glu) in exon 6 and a polymorphism NM_000388.4:c.1192G>A p. (Asp398Asn) in exon 4. The G557E mutation has been previously reported in a Japanese family in which all family members with the mutation had Ca/Cr below 0.01 consistent with FHH. The biochemical profile of FHH and PHPT may overlap. Our FHH patient with a G557E CaSR mutation illustrates that the differential diagnosis can be difficult in an index case with no family history, (false) positive parathyroid imaging and higher calciuria than expected for FHH. Calcium intake, vitamin D status and bone resorption might have contributed to the Ca/Cr variations over a 13-year clinical follow up. This case thus emphasizes the irreplaceable role of genetic testing of the CaSR gene when clinical evaluation is inconclusive.

scholarly journals Primary Hyperparathyroidism in Pregnancy: A Two-Case Report and Literature Review

2015 ◽  
Vol 2015 ◽  
pp. 1-3 ◽  
Author(s):  
A. D. Herrera-Martínez ◽  
R. Bahamondes-Opazo ◽  
R. Palomares-Ortega ◽  
C. Muñoz-Jiménez ◽  
M. A. Gálvez-Moreno ◽  
...  
Keyword(s):  
Case Report ◽  
Surgical Treatment ◽  
Early Diagnosis ◽  
Literature Review ◽  
Primary Hyperparathyroidism ◽  
Serum Levels ◽  
Second Trimester ◽  
Uncommon Disease ◽  
Fetal Complications ◽  
In Pregnancy

Primary hyperparathyroidism (PHPT) in pregnant women is an uncommon disease. It could be easily misdiagnosed because of physiologic changes during pregnancy; in some cases, patients could remain asymptomatic maintaining elevated calcium serum levels, and this situation represents a threat to the health of both mother and fetus. We present two cases of PHPT during pregnancy and their evolution after surgical treatment in the second trimester; there were no observed complications during pregnancy or delivery in our patients. Early diagnosis and medical/surgical treatment in PHPT are necessary for avoiding maternal and fetal complications which could not be predicted based on duration or severity of hypercalcemia. An appropriate management of PHPT during pregnancy is necessary for preserving the health of both the woman and the fetus.

scholarly journals Presentation, diagnostic assessment and surgical outcomes in primary hyperparathyroidism: a single centre’s experience

2018 ◽  
Vol 7 (10) ◽  
pp. 1105-1115 ◽  
Author(s):  
Laura J Reid ◽  
Bala Muthukrishnan ◽  
Dilip Patel ◽  
Mike S Crane ◽  
Murat Akyol ◽  
...  
Keyword(s):  
Primary Hyperparathyroidism ◽  
Clinical Features ◽  
Surgical Outcomes ◽  
Imaging Modality ◽  
Evidence Base ◽  
University Hospital ◽  
Clearance Ratio ◽  
Curative Surgery ◽  
History Of ◽  
Surgical Failure

Objective Primary hyperparathyroidism (PHPT) is a common reason for referral to endocrinology but the evidence base guiding assessment is limited. We evaluated the clinical presentation, assessment and subsequent management in PHPT. Design Retrospective cohort study. Patients PHPT assessed between 2006 and 2014 (n = 611) in a university hospital. Measurements Symptoms, clinical features, biochemistry, neck radiology and surgical outcomes. Results Fatigue (23.8%), polyuria (15.6%) and polydipsia (14.9%) were associated with PHPT biochemistry. Bone fracture was present in 16.4% but was not associated with biochemistry. A history of nephrolithiasis (10.0%) was associated only with younger age (P = 0.006) and male gender (P = 0.037). Thiazide diuretic discontinuation was not associated with any subsequent change in calcium (P = 0.514). Urine calcium creatinine clearance ratio (CCCR) was <0.01 in 18.2% of patients with confirmed PHPT. Older age (P < 0.001) and lower PTH (P = 0.043) were associated with failure to locate an adenoma on ultrasound (44.0% of scans). When an adenoma was identified on ultrasound the lateralisation was correct in 94.5%. Non-curative surgery occurred in 8.2% and was greater in those requiring more than one neck imaging modality (OR 2.42, P = 0.035). Conclusions Clinical features associated with PHPT are not strongly related to biochemistry. Thiazide cessation does not appear to attenuate hypercalcaemia. PHPT remains the likeliest diagnosis in the presence of low CCCR. Ultrasound is highly discriminant when an adenoma is identified but surgical failure is more likely when more than one imaging modality is required.

scholarly journals SAT-361 Familial Hypocalciuric Hypercalcemia Type 3: AP2S1 Mutation

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sarah Elizabeth Kerut ◽  
Licy L Yanes Cardozo
Keyword(s):  
Vitamin D ◽  
Primary Hyperparathyroidism ◽  
Parathyroid Gland ◽  
Genetic Mutation ◽  
Urinary Calcium ◽  
Familial Hypocalciuric Hypercalcemia ◽  
Dexa Scan ◽  
High Calcium ◽  
History Of ◽  
Type 3

Abstract Background: Familial hypocalciuric hypercalcemia (FHH) type 3 can appear similar to primary hyperparathyroidism and make the diagnosis of etiology of hypercalcemia challenging. Clinical Case: A 45-year-old man with hypertension and glaucoma was evaluated in clinic for hypercalcemia. His calcium was 12.3 mg/dL (8.4–10.2), PTH 41.9 pg/mL (15–65), Vitamin D 14.8 ng/mL (6.6–49) and phosphorus 1.7 mg/dL (2.7–4.5). He denied history of thiazide diuretic use, fragility fracture, nephrolithiasis and family history of calcium disorders. Further workup revealed normal kidney function, undetectable PTH related peptide and dual-energy x-ray absorptiometry (DEXA) scan with a T-score of -3.3 at spine L1-L4, -2.7 at femoral neck and -2.1 at distal one-third forearm. A 24-hour urine collection revealed a urinary calcium of 42.4 mg/24-hour (100–300) and calcium: creatinine clearance ratio of 0.003. Diagnosis of primary hyperparathyroidism was made despite low urinary calcium as this was thought to be due to vitamin D deficiency. Sestamibi scintigraphy and four-dimensional computed tomography did not localize a parathyroid adenoma, however, the patient was sent to surgery for four gland parathyroid exploration for primary hyperparathyroidism in setting of high calcium and young age with evidence of end-organ failure of osteoporosis. During surgery, three large abnormal parathyroid glands were identified and one normal parathyroid gland. Patient had a three-gland parathyroidectomy with intraoperative drop in PTH by 26.5%. Pathology returned as benign parathyroid tissues. After surgery, patient had persistently elevated calcium level of 12.6 mg/dL and an inappropriately non-suppressed PTH. He was then started on bisphosphonate and cinacalcet for osteoporosis and hypercalcemia, respectively and sent for genetic testing of FHH. His CASR gene was negative but his AP2S1 gene was positive which confirmed the diagnosis of FHH type 3. His calcium responded well to cinacalcet and repeat DEXA scan showed stability of bone mineral density in spine and hip after two years of treatment with bisphosphonate therapy. Conclusion: Familial hypocalciuric hypercalcemia type 3 is caused by an inactivating mutation in the AP2S1 gene. This gene encodes the adaptor-related protein complex 2, sigma 1 subunit which is located downstream from calcium-sensing receptor. This genetic mutation can appear similar to primary hyperparathyroidism in that it produces high levels of calcium and PTH and low phosphorus. Hypercalcemia, however, persists despite removal of parathyroid gland. This genetic mutation can be treated with cinacalcet in patients with high levels of calcium (&gt;1 upper limit of normal) or symptoms of hypercalcemia.

scholarly journals Atypical Presentation of Familial Hypocalciuric Hypercalcemia: Case Report

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A182-A183
Author(s):  
Dalal S Ali ◽  
Karel Dandurand ◽  
Aliya Aziz Khan
Keyword(s):  
Vitamin D ◽  
Primary Hyperparathyroidism ◽  
Dna Analysis ◽  
Receptor Gene ◽  
Familial Hypocalciuric Hypercalcemia ◽  
Calcium Sensing Receptor ◽  
Clearance Ratio ◽  
Subtotal Parathyroidectomy ◽  
Casr Gene ◽  
Calcium Sensing

Abstract Background: Differentiation between familial hypocalciuric hypercalcemia (FHH) and primary hyperparathyroidism (PHPT) can be challenging in certain cases in the absence of DNA analysis of the calcium sensing receptor gene. The distinction between those two clinical entities with overlapping biochemical features therefore relies on the calcium to creatinine clearance ratio (CCCR), which is expected to be low in FHH (&lt;0.01 in 80% of cases and between 0.01 and 0.02 in approximately 20% of patients)1. Patients with PHPT usually have a CCCR of&gt;= 0.02. A lower CCCR between 0.01 and 0.02 can be seen in approximately 20% of patients1,2and is more commonly seen in the presence of vitamin D insufficiency, impaired renal function, low calcium intake or being of African descent. It is advised to stop drugs which can contribute to hypercalcemia and lower the CCCR such as thiazide diuretics prior to evaluating the CCCR. Clinical Case: A 56-year-old lady was referred for evaluation of persistent hypercalcemia post parathyroidectomy and fatigue. She had mildly elevated ionized serum calcium (iCa) and a mid-normal PTH with a CCCR of 0.024. She had a normal BMD with no prior fragility fractures and passed a kidney stone prior to her presentation. Physical exam was unremarkable. She had previously travelled to Tampa and had a subtotal parathyroidectomy 3 glands (RU, LU, RL) for a possible diagnosis of PHPT, tissue biopsy showed hyperplastic parathyroids. Her MEN1 gene analysis was negative for MEN1 mutation and MRI of the abdomen was unremarkable. Her mother had a diagnosis of PHPT and osteoporosis. The iCa remained mildly elevated at 1.43 mmol/L (1.15–1.3) with a 24 hr urinary CCCR at 0.024 and a mid-normal PTH of 4.4 pmol/L (1.6–6.9). Her eGFR was 104 mls/min, 25 vitamin D 82 nmol/L (75–250), 1,25 dihydroxy vitamin D 122 pmol/L (60–206), PO4 0.90 mmol/L (0.8–1.45) and alkaline phosphatase 46 U/L (35–120) were all normal. She continued to have mild symptoms of hypercalcemia and her bone scan was negative for underlying skeletal pathology. DNA studies for mutations in the CaSR gene were completed. This confirmed the presence of a heterozygous loss of function mutation in the CASR gene at c493-2A&gt;G which appears to be pathogenic. Conclusion: The CCCR is useful in differentiating PHPT from FHH however in certain cases of FHH the CCCR may be higher then expected and we have now confirmed the presence of FHH with a molecular diagnosis in a patient with a CCCR as high as 0.02. References: 1 Gunn, IR, Gaffney, D. Clinical and laboratory features of calcium-sensing receptor disorders: a systematic review. Ann Clin Biochem 2004; 41:441–58 2 Stephen J. Marx, Letter to the Editor: Distinguishing Typical Primary Hyperparathyroidism From Familial Hypocalciuric Hypercalcemia by Using an Index of Urinary Calcium, The Journal of Clinical Endocrinology & Metabolism, 2015

scholarly journals Persistent hypercalcemia with similar familial Hypocalciuric hypercalcemia features: a case report and literature review

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maryam Zahedi ◽  
Reyhane Hizomi Arani ◽  
Maryam Rafati ◽  
Atieh Amouzegar ◽  
Farzad Hadaegh
Keyword(s):  
Vitamin D ◽  
Laboratory Data ◽  
Vitamin D Supplementation ◽  
Dietary Calcium Intake ◽  
Familial Hypocalciuric Hypercalcemia ◽  
Normal Range ◽  
Clearance Ratio ◽  
Vitamin D Levels ◽  
History Of ◽  
25 Oh Vitamin D

Abstract Background Primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcemia (FHH) are the most important differential diagnosis of parathyroid hormone (PTH)-dependent hypercalcemia. The clinical features of FHH and PHPT can overlap in some cases. Therefore, these two diseases must be differentiated to prevent unnecessary parathyroidectomy. Here, we present a case that was not entirely matched with any of the known differential diagnoses of hypercalcemia. Case presentation A 19-year-old girl with no history of any disease presented with persistent hypercalcemia without any specific musculoskeletal complaint. We found persistent hypercalcemia in her routine laboratory data from 3 years ago; while no data was available during the childhood period. Her dietary calcium intake was normal. She did not mention any history of renal stone, bone fracture as well as family history of hypercalcemia. Biochemical features showed normal values of serum creatinine, high normal serum calcium (range, 10.3–11.3 mg/dL; (normal range: 8.8–10.4)), and non-suppressed PTH levels (range, 37.2–58.1 pg/mL; (normal range: 10–65)). Serum 25 OH vitamin D level at the first visit was 16.1 ng/mL that treated by vitamin D supplementation. Since then, all 25 OH vitamin D levels were in the acceptable range. After correction of vitamin D deficiency during the follow-up period the calcium creatinine clearance ratio(s) (CCCR) were calculated in the range of 0.009 to 0.014 (means below 1%). The clinical and laboratory data indicate more FHH rather than PHPT. Genetic studies were negative for the common genes associated with FHH (CASR, GNA11, and AP2S1 genes) and multiple endocrine neoplasia type1 (MEN1). On the other hand, no evidence of autoimmunity was found in her to support an autoimmune FHH-like syndrome. Hence, the case did not match completely to any diagnosis of FHH and PHPT, so we decided to follow her. Conclusion We presented a patient with FHH phenotype whose common genetic tests were negative. Further research is needed to ascertain other causes leading to similar manifestations.

scholarly journals Primary Hyperparathyroidism in Pregnancy: Literature Review of the Diagnosis and Management

2021 ◽  
Vol 10 (13) ◽  
pp. 2956
Author(s):  
Dalal S. Ali ◽  
Karel Dandurand ◽  
Aliya A. Khan
Keyword(s):  
Primary Hyperparathyroidism ◽  
Case Reports ◽  
Safety Data ◽  
Case Series ◽  
Close Monitoring ◽  
Management Options ◽  
Diagnosis And Management ◽  
Severe Hypercalcemia ◽  
Fetal Complications ◽  
In Pregnancy

Background: Parathyroid disease is uncommon in pregnancy. During pregnancy, multiple changes occur in the calcium regulating hormones which may make the diagnosis of primary hyperparathyroidism more challenging. Close monitoring of serum calcium during pregnancy is necessary in order to optimize maternal and fetal outcomes. In this review, we will describe the diagnosis and management of primary hyperparathyroidism during pregnancy. Methods: We searched MEDLINE, CINAHL, EMBASE and Google scholar bases from 1 January 1990 to 31 December 2020. Case reports, case series, book chapters and clinical guidelines were included in this review. Conclusions: Medical management options for primary hyperparathyroidism during pregnancy are severely limited due to inadequate safety data with the various potential therapies available, and surgery is advised during the 2nd trimester of pregnancy in the presence of severe hypercalcemia (calcium adjusted for albumin greater than 3.0 mmol/L (12.0 mg/dL)). Hypercalcemia should be avoided during pregnancy in order to minimize maternal and fetal complications.

Plasma active and inactive renin and fetal complications in women with high risk pregnancies

1991 ◽  
Vol 69 (9) ◽  
pp. 1321-1326 ◽  
Author(s):  
Paola Ferraris ◽  
Patrizia Quorso ◽  
Gabriella Gazzano ◽  
Massimo Cianci ◽  
Carla Sala ◽  
...  
Keyword(s):  
High Risk ◽  
Clinical History ◽  
Fetal Outcome ◽  
Normal Weight ◽  
Second Trimester ◽  
Term Infants ◽  
Active Renin ◽  
Fetal Complications ◽  
History Of ◽  
Inactive Renin

To examine whether the activation of the renin system, which occurs during pregnancy, may be relevant for the development and the outcome of the fetus, we measured active and inactive renin throughout gestation in 29 women having a pregnancy defined as "high risk" because of a clinical history of hypertension, nephropathy, and unexplained abortions. In 23 of these women who delivered full-term infants with normal weight and status, we found that active renin increased progressively from early pregnancy until the end of the second trimester and then declined slightly thereafter. In contrast, in the remaining six women who had fetal complications consisting of either signs of distress requiring cesarean section or growth retardation, the increase in active renin failed to occur. In all women the levels of inactive renin were more elevated throughout gestation than those observed in nonpregnant women, and were higher, although not significantly, in women without fetal complications than in those with fetal complications. Thus, a blunted activation of the renin system during pregnancy is associated with alteration in fetal development and may possibly contribute to it.Key words: active and inactive renin, pregnancy, fetal outcome.

scholarly journals Curative resection of an aldosteronoma causing primary aldosteronism in the second trimester of pregnancy

2020 ◽  
Vol 2020 ◽  
Author(s):  
Skand Shekhar ◽  
Rasha Haykal ◽  
Crystal Kamilaris ◽  
Constantine A Stratakis ◽  
Fady Hannah-Shmouni
Keyword(s):  
Primary Aldosteronism ◽  
Secondary Hypertension ◽  
Uncontrolled Hypertension ◽  
List Type ◽  
Second Trimester ◽  
Unilateral Adrenalectomy ◽  
Fetal Complications ◽  
Common Etiology ◽  
History Of ◽  
In Pregnancy

Summary A 29-year-old primigravida woman with a known history of primary aldosteronism due to a right aldosteronoma presented with uncontrolled hypertension at 5 weeks of estimated gestation of a spontaneous pregnancy. Her hypertension was inadequately controlled with pharmacotherapy which lead to the consideration of surgical management for her primary aldosteronism. She underwent curative right unilateral adrenalectomy at 19 weeks of estimated gestational age. The procedure was uncomplicated, and her blood pressure normalized post-operatively. She did, however, have a preterm delivery by cesarean section due to intrauterine growth retardation with good neonatal outcome. She is normotensive to date. Learning points: Primary aldosteronism is the most common etiology of secondary hypertension with an estimated prevalence of 5–10% in the hypertensive population. It is important to recognize the subtypes of primary aldosteronism given that certain forms can be treated surgically. Hypertension in pregnancy is associated with significantly higher maternal and fetal complications. Data regarding the treatment of primary aldosteronism in pregnancy are limited. Adrenalectomy can be considered during the second trimester of pregnancy if medical therapy fails to adequately control hypertension from primary aldosteronism.

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