Normocalcemic and Normohormonal Primary Hyperparathyroidism: Laboratory Values and End-Organ Effects.

OBJECTIVE: Variants of primary hyperparathyroidism (pHPT), described as normocalcemic (NC) and normohormonal (NH), can confuse the diagnosis of classic pHPT. DATA SOURCES: A MEDLINE search was performed for variants of pHPT using the PubMed database (last queried October 2019). REVIEW METHODS: The search was restricted to articles published after 1960 that were specific to humans. Studies were included in our analysis if laboratory values and incidence of end-organ involvement were reported for NCpHPT and NHpHPT variants. The search returned 189 articles; 27 additional studies were identified and included for a total of 216. Non-English-language studies were excluded. Abstracts were screened, full-text articles were then assessed, and 82 articles were excluded. Data were pooled using a random-effects model in studies that compared NC or NH pHPT to classic pHPT. Comparative laboratory values are presented. CONCLUSION: This analysis compares NCpHPT and NHpHPT to classic pHPT. Nephrolithiasis was 21.7% (NCpHPT), 15.9% (classic pHPT), and 25.4% (NHpHPT). Decreased bone mineral density was 49.7% (NCpHPT), 39.7% (classic pHPT), and 40.3% (NHpHPT). Fractures in the NCpHPT group were not significantly different from the classic pHPT. Hypertension in the NCpHPT group was significantly less than classic pHPT (odds ratio, 0.59; 95% CI, 0.40-0.88). IMPLICATIONS FOR CLINICAL PRACTICE: This information may serve to inform clinicians of the laboratory subtleties of these variants that are being seen with greater frequency in contemporary practice.

PRIMARY HYPERPARATHYROIDISM, WITH A FOCUS ON MANAGEMENT OF THE NORMOCALCEMIC FORM: TO TREAT OR NOT TO TREAT?

OBJECTIVE: The aim of this study was to determine reasonable care for normocalcemic primary hyperparathyroidism (NCPHPT) patients treated at the endocrine clinic. METHODS: The study is based on 218 outpatient cases of primary hyperparathyroidism (PHPT), 187 (86%) of whom were NCPHPT. Subjective complaints, biochemical tests, imaging, and treatment outcome for NCPHPT patients were monitored and compared with the same parameters in patients with hypercalcemic hyperparathyroidism. The number of patients with newly diagnosed NCPHPT who became hypercalcemic and the time period in which it happened were also recorded. RESULTS: Over 6 years of study, in total, 36 of 187 originally normocalcemic patients became hypercalcemic (19%); 24 of 36 within 2 years and 2 of 36 later than after 4 years. Sestamibi scintigraphy was performed in 103 normocalcemic patients (adenoma was detected in 5 cases) and in 46 hypercalcemic patients with pathologically elevated serum calcium levels at the time of assessment (adenoma was detected in 32 of 46 cases). Surgery was performed in 33 patients, 11 of whom were originally normocalcemic (i.e., 6% of all 187 originally normocalcemic patients), and 22 were hypercalcemic from the outset (i.e., 71% of all 31 originally hypercalcemic patients). CONCLUSION: Some NCPHPT patients converted to hypercalcemic, mostly within 2 years, but some after 4 years or later. Normocalcemic patients should be monitored on a long-term basis, as it is impossible to anticipate when and which normocalcemic patients will become hypercalcemic. Imaging is much less effective in normocalcemic than in hypercalcemic patients.

Parathyroid adenoma with coeliac disease: primary or quaternary hyperparathyroidism?

Coeliac disease is a gluten-sensitive enteropathy of varying severity. Osteomalacia and hypocalcaemia can result from malabsorption of vitamin D and calcium, which, in turn, can lead to secondary hyperparathyroidism. If coeliac disease remains untreated for long, tertiary hyperparathyroidism can also develop through autonomy of the parathyroid glands via chronic stimulation. Primary hyperparathyroidism also has been reported in some cases of coeliac disease. We report the case of an adolescent with coeliac disease presenting with severe hypercalcaemia from a parathyroid adenoma. A 14 year-old girl was admitted to our department for delayed puberty and growth retardation. Laboratory examination revealed iron deficiency anaemia, low 25OH vitamin D level (7 ng/ml), high parathyroid hormone level (PTH) (955 pg/ml), and hypercalcaemia (13.4 mg/dl). Endoscopic biopsy was compatible with gluten enteropathy. Endomysium antibody was positive. A gluten-free diet was started. Her calcium returned to normal after excision of the parathyroid adenoma. After four months of the gluten-free diet, she began to mature, and puberty began with development of breasts and axillary-pubic hair growth. It has been suggested that autonomous four-gland hyperplasia or tertiary hyperparathyroidism may progress to adenoma formation, and that this should be termed "quaternary hyperparathyroidism". More studies are required to explain the relationship between coeliac disease and hyperparathyroidism.

Should 'mild primary hyperparathyroidism' be reclassified as 'insidious': is it time to reconsider?

Primary hyperparathyroidism (PHPT) is a common incidental finding on routine biochemical testing, affecting around 1% of the population. The majority of individuals will be asymptomatic at diagnosis, with no evidence of end organ damage, and unless individuals aged <50 years at diagnosis, they are often considered to have 'mild' PHPT, as they do not meet published criteria for parathyroidectomy (PTX). However, there is increasing evidence that 'mild' PHPT is associated with adverse health outcomes. Long-term observational studies describing the natural history of 'mild' PHPT suggest that even though biochemistry may be relatively stable in the majority, bone mineral density (BMD) does decline after approximately 10 years of observation, whereas significant improvements in BMD are seen following PTX. Recent large European record linkage studies of 'mild PHPT' demonstrate significantly increased all-cause and cardiovascular mortality, similar to rates published for patients with PHPT who meet the NIH surgical criteria. 'Mild' PHPT was also associated with increased admissions for nonfatal cardiovascular disease, renal failure, renal stones, fractures, hypertension, psychiatric disease, cancer and diabetes, suggesting that 'insidious' PHPT may be a more appropriate description, or at least that the term 'mild' should be abandoned. Randomized controlled trials (RCTs) have begun to explore the benefits of PTX in this condition, demonstrating improvements in BMD and some psychiatric outcomes at approximately 2 years of follow-up. However, larger, adequately powered, long-term, RCTs will be required to determine whether PTX improves potential long-term morbidity and mortality in patients with PHPT who do not meet standard surgical criteria.

Medication discontinuation after curative surgery for sporadic primary hyperparathyroidism.

BACKGROUND: Although parathyroidectomy (Ptx) for sporadic primary hyperparathyroidism (PH) improves comorbidities and symptoms, routine Ptx for minimally symptomatic PH remains controversial. Whether successful Ptx translates into discontinuation or dose-reduction of prescribed medications is unknown. METHODS: Consecutive patients undergoing curative Ptx for sporadic PH from January 2007 to April 2009 were compared to patients undergoing thyroidectomy (Tx). We reviewed patient demographics, symptoms, comorbid conditions, and pre- and postoperative medications utilizing the Fisher exact test and t test for comparisons. RESULTS: Compared to 176 Tx patients, 260 Ptx patients were older (P < .001), more commonly men (P = .006), and had higher preoperative prevalences of every examined PH symptom and comorbid condition. Postoperatively, even minimal PH symptoms improved after Ptx. The mean number of preoperative medications was higher in Ptx patients (4 vs 2.8, P < .001). Discontinuation or dose-reduction of medication occurred in 28 (11%) Ptx patients vs 7 (4%) Tx patients (P = .01). After Ptx, symptom improvement was the predominant reason for beneficial medication changes, and the most common beneficial effect was discontinuation or dose-reduction of chronic analgesics (33%). CONCLUSION: PH symptoms are numerous and improve after curative Ptx. Medication use for related symptoms can be beneficially reduced by surgery. Drug profiles should be routinely reviewed and adjusted after parathyroidectomy.

Normocalcemic primary hyperparathyroidism.

Primary hyperparathyroidism is a common disorder of mineral metabolism characterized by incompletely regulated, excessive secretion of parathyroid hormone from one or more of the parathyroid glands. The historical view of this disease describes two distinct entities marked by two eras. When primary hyperparathyroidism was first discovered about 80 years ago, it was always symptomatic with kidney stones, bone disease and marked hypercalcemia. With the advent of the multichannel autoanalyzer about 40 years ago, the clinical phenotype changed to a disorder characterized by mild hypercalcemia and the absence of classical other features of the disease. We may now be entering a 3rd era in the history of this disease in which patients are being discovered with normal total and ionized serum calcium concentrations but with parathyroid hormone levels that are consistently elevated. In this article, we describe this new entity, normocalcemic primary hyperparathyroidism, a forme fruste of the disease.

Normocalcemic primary hyperparathyroidism / Hiperparatiroidismo normocalcêmico primário

Primary hyperparathyroidism is a common disorder of mineral metabolism characterized by incompletely regulated, excessive secretion of parathyroid hormone from one or more of the parathyroid glands. The historical view of this disease describes two distinct entities marked by two eras. When primary hyperparathyroidism was first discovered about 80 years ago, it was always symptomatic with kidney stones, bone disease and marked hypercalcemia. With the advent of the multichannel autoanalyzer about 40 years ago, the clinical phenotype changed to a disorder characterized by mild hypercalcemia and the absence of classical other features of the disease. We may now be entering a 3rd era in the history of this disease in which patients are being discovered with normal total and ionized serum calcium concentrations but with parathyroid hormone levels that are consistently elevated. In this article, we describe this new entity, normocalcemic primary hyperparathyroidism, a forme fruste of the disease.

O hiperparatiroidismo primário (HPTP) é uma doença comum caracterizada por uma regulação inadequada da secreção do paratormônio em uma ou mais glândulas paratiroides. Historicamente a doença pode ser dividida em duas eras. Quando o HPTP foi descoberto há 80 anos, era sempre sintomático com nefrolitíase, doença óssea e acentuada hipercalcemia. Com o advento das rotinas laboratoriais por autoanalisadores bioquímicos há 40 anos, o fenótipo clínico mudou para uma doença sintomaticamente leve na ausência daqueles achados clássicos. Está se entrando numa terceira era em que os pacientes são diagnosticados com calcemia normal na presença de níveis circulantes elevados do paratormônio. Neste artigo, descreve-se essa nova entidade, hiperparatiroidismo primário normocalcêmico, uma forma frusta da doença.