-
Current Opinion in Endocrinology,... Feb 2024Primary mitochondrial diseases are one of the most prevalent groups of multisystem genetic disorders. Endocrinopathies associated with mitochondrial diseases may have... (Review)
Review
PURPOSE OF REVIEW
Primary mitochondrial diseases are one of the most prevalent groups of multisystem genetic disorders. Endocrinopathies associated with mitochondrial diseases may have clinical features that are distinct from the more common forms. We provide an overview of mitochondrial disorder genetics and phenotypes, focusing on recent studies regarding identification and treatment of associated endocrinopathies.
RECENT FINDINGS
Known endocrine phenotypes of mitochondrial disorders continue to expand, and now include growth hormone deficiency, hypogonadism, precocious puberty, hypoparathyroidism, hypo- and hyperthyroidism, diabetes, and adrenal insufficiency. Recent studies suggest several genotype-phenotype correlations, including those related to nuclear variants. Diagnosis is important, as special considerations should be made in the management of endocrinopathies in mitochondrial patients. Finally, new mitochondrial replacement strategies may soon be available for women interested in preventing mitochondrial disease transmission to offspring.
SUMMARY
Patients with multiple endocrinopathies or atypical endocrinopathies should be evaluated for primary mitochondrial disease, as a diagnosis may impact management of these individuals.
Topics: Humans; Female; Endocrine System Diseases; Diabetes Mellitus; Puberty, Precocious; Mitochondrial Diseases; Hyperthyroidism; Adrenal Insufficiency
PubMed: 38047549
DOI: 10.1097/MED.0000000000000848 -
Clinical Immunology (Orlando, Fla.) Oct 2023Paired box 1 (PAX1) deficiency has been reported in a small number of patients diagnosed with otofaciocervical syndrome type 2 (OFCS2). We described six new patients who...
Paired box 1 (PAX1) deficiency has been reported in a small number of patients diagnosed with otofaciocervical syndrome type 2 (OFCS2). We described six new patients who demonstrated variable clinical penetrance. Reduced transcriptional activity of pathogenic variants confirmed partial or complete PAX1 deficiency. Thymic aplasia and hypoplasia were associated with impaired T cell immunity. Corrective treatment was required in 4/6 patients. Hematopoietic stem cell transplantation resulted in poor immune reconstitution with absent naïve T cells, contrasting with the superior recovery of T cell immunity after thymus transplantation. Normal ex vivo differentiation of PAX1-deficient CD34 cells into mature T cells demonstrated the absence of a hematopoietic cell-intrinsic defect. New overlapping features with DiGeorge syndrome included primary hypoparathyroidism (n = 5) and congenital heart defects (n = 2), in line with PAX1 expression during early embryogenesis. Our results highlight new features of PAX1 deficiency, which are relevant to improving early diagnosis and identifying patients requiring corrective treatment.
Topics: Humans; Paired Box Transcription Factors; Phenotype; T-Lymphocytes; Thymus Gland; Severe Combined Immunodeficiency
PubMed: 37689091
DOI: 10.1016/j.clim.2023.109757 -
JAMA Network Open May 2024Hypoparathyroidism following thyroid surgery is a serious complication that occurs frequently when surgery is performed by low-volume thyroid surgeons without experience...
IMPORTANCE
Hypoparathyroidism following thyroid surgery is a serious complication that occurs frequently when surgery is performed by low-volume thyroid surgeons without experience in parathyroid surgery.
OBJECTIVE
To evaluate the occurrence of hypoparathyroidism following total thyroidectomy after the introduction of autofluorescence in low-volume, nonparathyroid institutions.
DESIGN, SETTING, AND PARTICIPANTS
This prospective, multicenter cohort study, with a follow-up period of up to 1 year, was conducted in Denmark at 2 low-volume nonparathyroid institutions between January 2021 and November 2023. All adult patients referred for total thyroidectomy were assessed for eligibility (n = 90). Only patients with no history of thyroid surgery were considered (n = 89). Patients who only underwent lobectomy (n = 6) or declined to participate (n = 5) were excluded. All included patients completed follow-up. The prospective cohort was compared with a historical cohort of successive patients undergoing primary total thyroidectomy from 2016 to 2020 (before autofluorescence was available).
INTERVENTION
Included patients underwent autofluorescence-guided total thyroidectomy.
MAIN OUTCOMES AND MEASURES
Rate of hypoparathyroidism. Immediate hypoparathyroidism was defined as the need for active vitamin D postoperatively, whereas permanent hypoparathyroidism was considered when there still was a need for active vitamin D 1 year after surgery.
RESULTS
Seventy-eight patients underwent autofluorescence-guided surgery (mean [SD] age, 55.6 [13.1] years; 67 [86%] female) and were compared with 89 patients in the historical cohort (mean [SD] age, 49.7 [12.8] years; 78 [88%] female). The rate of immediate hypoparathyroidism decreased from 37% (95% CI, 27%-48%) to 19% (95% CI, 11%-30%) after the introduction of autofluorescence (P = .02). Permanent hypoparathyroidism rates decreased from 32% (95% CI, 22%-42%) to 6% (95% CI, 2%-14%) (P < .001), reaching 0% at the end of the study. More parathyroid glands were identified with autofluorescence (75% [95% CI, 70%-80%] vs 61% [95% CI, 56%-66%]) (P < .001) and less parathyroid glands were inadvertently excised (4% [95% CI, 1%-11%] vs 21% [95% CI, 13%-31%]) (P = .001).
CONCLUSIONS AND RELEVANCE
In this cohort study of autofluorescence-guided thyroid surgery in low-volume, nonparathyroid institutions, the use of autofluorescence was associated with a significant decrease in both immediate and permanent hypoparathyroidism. When autofluorescence was used, hypoparathyroidism rates were comparable with those of high-volume surgeons who also perform parathyroid surgery.
Topics: Humans; Thyroidectomy; Hypoparathyroidism; Female; Male; Middle Aged; Prospective Studies; Postoperative Complications; Adult; Denmark; Optical Imaging; Aged; Surgery, Computer-Assisted
PubMed: 38748422
DOI: 10.1001/jamanetworkopen.2024.11384 -
Endocrine Connections Sep 2023Total thyroidectomy is associated with a high risk of postoperative hypoparathyroidism, mainly due to the unintended surgical damage to the parathyroid glands or their...
OBJECTIVE
Total thyroidectomy is associated with a high risk of postoperative hypoparathyroidism, mainly due to the unintended surgical damage to the parathyroid glands or their blood supply. It is possible that surgeons who also perform parathyroid surgery see lower rates of postoperative hypoparathyroidism. In a single institution, we investigated the effects of restricting total thyroidectomy operations for Graves' disease to two surgeons who performed both thyroid and parathyroid surgeries. We aimed to evaluate the rates of postoperative hypoparathyroidism in a 10-year period with primary attention toward patients with Graves' disease.
DESIGN
Retrospective cohort study from a single institution.
METHODS
We defined the rate of permanent hypoparathyroidism after total thyroidectomy as the need for active vitamin D 6 months postoperatively. Between 2012 and 2016, seven surgeons performed all thyroidectomies. From January 2017, only surgeons also performing parathyroid surgery carried out thyroidectomies for Graves' disease.
RESULTS
We performed total thyroidectomy in 543 patients. The rate of permanent hypoparathyroidism decreased from 28% in 2012-2014 to 6% in 2020-2021. For patients with Graves' disease, the rate of permanent hypoparathyroidism decreased from 36% (13 out of 36) in 2015-2016 to 2% (1 out of 56) in 2020-2021. In cancer patients, the rate of permanent hypoparathyroidism decreased from 30% (14 out of 46) in 2012-2014 to 10% (10 out of 51) in 2020-2021.
CONCLUSION
Restricting thyroidectomy to surgeons who also performed parathyroid operations reduced postoperative hypoparathyroidism markedly. Accordingly, we recommend centralisation of the most difficult thyroid operations to centres and surgeons with extensive experience in parathyroid surgery.
SIGNIFICANCE STATEMENT
Thyroid surgery is performed by many different surgeons with marked differences in outcome. Indeed, the risk of postoperative permanent hypoparathyroidism may be very high in low-volume centres. This serious condition affects the quality of life and increases long-term morbidity and the patients develop a life-long dependency of medical treatments. We encountered a high risk of hypoparathyroidism after the operation for Graves' disease and restricted the number of surgeons to two for these operations. Further, these surgeons were experienced in both thyroid and parathyroid surgeries. We show a dramatic reduction in postoperative hypoparathyroidism after this change. Accordingly, we recommend centralisation of total thyroidectomy to surgeons with experience in both thyroid and parathyroid procedures.
PubMed: 37487033
DOI: 10.1530/EC-23-0198 -
Endocrine Journal Jan 2024Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) in several organs including endocrine glands. Among endocrine irAEs, thyroid and... (Review)
Review
Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) in several organs including endocrine glands. Among endocrine irAEs, thyroid and pituitary irAEs are frequently observed, followed by primary adrenal insufficiency, insulin-dependent diabetes mellitus, and hypoparathyroidism. These conditions could lead to life-threatening consequences, such as adrenal crisis and diabetic ketoacidosis. On the other hand, several types of irAEs including thyroid and pituitary irAEs are reported to be associated with better overall survival. Therefore, it is important to understand and manage endocrine irAEs, which differ depending on the ICI regimen used. In this review, we describe the clinical features, potential biomarkers, management strategies, and possible mechanisms of thyroid and pituitary irAEs.
Topics: Humans; Thyroid Gland; Pituitary Gland; Pituitary Diseases; Biomarkers; Diabetes Mellitus, Type 1; Neoplasms
PubMed: 37940567
DOI: 10.1507/endocrj.EJ23-0524 -
AME Case Reports 2024Familial hypocalciuric hypercalcemia (FHH) is a hypercalcemic syndrome that is usually characterized by uncomplicated hypercalcemia and normal longevity. The inheritance...
BACKGROUND
Familial hypocalciuric hypercalcemia (FHH) is a hypercalcemic syndrome that is usually characterized by uncomplicated hypercalcemia and normal longevity. The inheritance pattern is autosomal dominant with high penetrance, and it affects both men and women equally. FHH is caused by mutations that disturb the normal functioning of the calcium-sensing receptor () gene. This causes a general lack of sensitivity to calcium, eventually leading to hypercalcemia and low calcium levels in the urine.
CASE DESCRIPTION
We report a case of a healthy 24-year-old female with longstanding hypercalcemia and a family history indicating asymptomatic hypercalcemia. The patient was also asymptomatic and had no significant past medical or surgical history. Laboratory investigations and the genetic study revealed findings suggestive of FHH subtype 1.
CONCLUSIONS
The phenotype of FHH is normal, and symptoms of hypercalcemia are usually not present. Patients with FHH and hypoparathyroidism have lower calcium clearance than controls with hypoparathyroidism. This shows that relative hypocalciuria in FHH is not caused by hyperparathyroidism. Since calcium does not appropriately suppress or affect the parathyroid glands in FHH, this means that FHH is a disorder of abnormal transport of extracellular calcium and/or response to it in at least two organs, the parathyroid gland and the kidney. It is quite similar to primary hyperparathyroidism (pHPT) biochemically hence it is important to differentiate this condition from pHPT and hypercalcemia caused by other diseases to avoid any unnecessary surgical or medical intervention.
PubMed: 38711891
DOI: 10.21037/acr-23-132 -
Cureus Sep 2023Hypoparathyroidism requires management with both calcium supplementation and active vitamin D to avert a state of hypocalcemia. During late gestation and the postpartum... (Review)
Review
Hypoparathyroidism requires management with both calcium supplementation and active vitamin D to avert a state of hypocalcemia. During late gestation and the postpartum period (specifically lactation), there is an under-recognized, yet intriguing occurrence of apparent 'pseudohyperparathyroidism', whereby supplementation dosages may need to either be reduced or discontinued, to prevent hypercalcemia. The explanation for this apparent phenomenon of improved parathyroid status ('remission' or 'resolution') is incompletely understood; the purpose of this review is to analyze the case reports of this enigma within the medical (and grey) literature, providing an overall pathophysiological explanation and recommendation for the management of such patients. A literature search was conducted through PubMed/Medline, CINAHL, Cochrane Library Database, Scopus, UpToDate, Google Scholar, and the grey literature without a time-restricted period, analyzing all available articles within the literature describing an apparent improvement in parathyroid status in late-gestation and postpartum (lactating) females. Non-hypoparathyroid case reports were also included to further analyze and synthesize an overall likely pathophysiological explanation. Through the literature search, 24 papers were identified covering such a phenomenon in patients with hypoparathyroidism, alongside multiple additional reports of a similar occurrence in patients without underlying hypoparathyroidism. The pathophysiology is believed to occur due to the placental production of parathyroid hormone-related peptide (PTHrP) during gestation, with further production from the lactating mammary glands during the postpartum period. A typical pattern is observed, with increased PTHrP and suppressed PTH throughout both gestation and lactation (present in both normal and hypoparathyroid subjects). The concept of PTHrP-induced hypercalcemia is further demonstrated in patients without hypoparathyroidism, including subjects with placental hypersecretion and mammary gland enlargement. It is evident that patients with hypoparathyroidism may require a dosage reduction during late gestation and lactation, due to the risk for hypercalcemia. In addition to patients with hypoparathyroidism, this pathophysiological phenomenon occurs in unsuspecting patients, demonstrating the need for all clinicians in contact with pregnant females to be aware of this uncommon - yet perilous - occurrence.
PubMed: 37790033
DOI: 10.7759/cureus.46123