CLINICAL AND LABORATORY CHARACTERISTICS OF PATIENTS WITH GESTATIONAL PRIMARY HYPERPARATHYROIDISM

SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 217 CLINICAL AND LABORATORY CHARACTERISTICS OF PATIENTS WITH GESTATIONAL PRIMARY HYPERPARATHYROIDISM N.T. Rikhsieva Associate Professor, Department of Internal Diseases, Alfraganus University, Republic of Uzbekistan, Tashkent https://doi.org/10.5281/zenodo.17860853 Abstacrt. Objective of the study: To perform a clinical and laboratory characterization of patients with gestational primary hyperparathyroidism (PHPT). The study included 11 women of reproductive age in whom primary hyperparathyroidism was first diagnosed during pregnancy (prospective observation, 2024). The average age of the examined patients was 30.2 ± 1.4 years. The control group consisted of 10 somatically healthy women of comparable age. The examination complex included:  General clinical methods — assessment of symptom severity using the PAS questionnaire;  Biochemical studies — determination of total calcium, inorganic phosphorus, vitamin D, bilirubin (total, direct, and indirect), urea, creatinine, ALT, AST, PTI, and other parameters;  Hormonal studies — measurement of thyroid-stimulating hormone (TSH) and parathyroid hormone (PTH) concentrations;  Instrumental methods — electrocardiography (ECG), ultrasound examination of the thyroid gland and internal organs, chest X-ray, and others. In patients with PHPT, a significant increase in the severity of clinical symptoms according to the PAS scale was observed compared to the control group. Analysis of biochemical and hormonal parameters revealed statistically significant intergroup differences: PTH concentrations in the main group were significantly higher (p < 0.0001), whereas vitamin D levels were significantly lower (p < 0.05). Conclusion 1. Primary hyperparathyroidism first detected during pregnancy is a clinically significant condition that may rapidly progress and adversely affect both the course of pregnancy and fetal development. 2. The treatment of PHPT during pregnancy is limited by diagnostic and therapeutic constraints. In cases of disease progression, surgical intervention is recommended, preferably during the second trimester, when the formation of major fetal organs is completed and the risk of preterm labor is reduced. 3. Careful monitoring of the maternal and fetal condition is required before surgery, and postpartum evaluation of calcium levels in the newborn is mandatory. Keywords: primary hyperparathyroidism, pregnancy, gestational complications, parathyroid hormone, vitamin D. Introduction. It is widely recognized that maintaining serum calcium levels is one of the body's key homeostatic functions. However, with the development of hypercalcemia screening programs both in our country and abroad, a significant prevalence of hypercalcemia is being SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 218 identified in the general population. In most cases, moderately elevated blood calcium levels are asymptomatic or have minimal clinical manifestations, posing no immediate threat to life. [1] However, severe hypercalcemia, regardless of the etiologic factor, has a destructive effect on the functioning of vital systems, primarily the central nervous system, kidneys, and cardiovascular system. Hypercalcemic crisis, characterized by a doubling of the upper limit of normal calcium levels, is associated with high mortality (30-60%). [2]. The severity and duration of hypercalcemia determine the risk of complications. Therefore, timely diagnosis of hypercalcemia and its etiology in women, especially during pregnancy, is of paramount importance. Failure to promptly treat hypercalcemia during pregnancy is associated with a high risk of complications, reaching 80% [3]. The most serious consequences include tetany and hypocalcemia in the newborn, spontaneous abortion, intrauterine fetal death, and preterm birth [4]. According to the authors, there is currently insufficient data to confidently state the benefits of calcium supplementation for key pregnancy outcomes. Therefore, the advisability of routine calcium supplementation by pregnant women remains unclear [5]. Furthermore, significant changes in maternal blood calcium concentrations can lead to serious disruptions in the fetal endocrine system, affecting the regulation of calcium metabolism and the development of glands such as the adrenal glands. Furthermore, calcium metabolism problems in the mother during pregnancy can significantly impact not only the development of hormonal calcium regulation and the development of the fetus's adrenal glands, but also their ability to adapt to environmental changes and regulate their circadian rhythms after birth. In pregnant women, primary hyperparathyroidism (PHPT) is a rare condition whose detection is difficult. This is due to the lack of standard screening for elevated calcium levels, as well as the physiological changes in calcium-phosphorus balance characteristic of pregnancy. The lack of clear, specific signs of PHPT further complicates diagnosis. Currently, there is no clearly developed strategy for managing pregnant women with this condition. [6]. It is generally understood that pregnancy with primary hyperparathyroidism (PHPT) is associated with an increased risk of maternal complications, such as hyperemesis gravidarum, nephrolithiasis, pancreatitis, spontaneous abortion, preeclampsia, and polyhydramnios. Neonatal sequelae, including hypocalcemia, tetany, intrauterine growth retardation, and perinatal mortality, have also been described [7]. Due to the relevance of the study, we analysed clinical cases of the disease. The aim of the study was to perform a clinical and laboratory characterization of patients with gestational primary hyperparathyroidism. Material and methods of the research. Eleven women of reproductive age (prospectively) with PHPT, first diagnosed during pregnancy, were examined between 2024 and 2025. The average age of the patients was 30.2 ± 1.4 years. The control group consisted of 10 healthy women of the same age. Inclusion criteria: pregnant women, hypercalcemia, PHPT, women of childbearing age. Exclusion criteria: children and adolescents, men, non-pregnant women. The research methods included general clinical (PAS questionnaire), biochemical (total calcium, phosphorus, vitamin D, bilirubin (direct and indirect), urea, creatinine, ALT, AST, PTI, etc.), hormonal (TSH, PHPT), and instrumental (ECG, thyroid ultrasound, internal organs, chest X-ray, etc.). The analysis included Russian recommendations for PHPT [8] and American guidelines for endocrine surgeons [9]. In 2002, J.L. Pasieka et al. [10] developed and implemented a method for assessing the results of surgical treatment for hyperparathyroidism. This tool allows SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 219 for measuring the frequency and severity of symptoms in patients. It assesses not only the presence of symptoms but also their intensity (on a scale from 0 to 100), allowing for the quantitative assessment of manifestations characteristic of hyperparathyroidism and the calculation of a total symptom score before and after parathyroidectomy (PTE). In the PAS questionnaire, the sum of scores for each column reflects the overall symptom level. Statistical calculations were performed in a Microsoft Windows environment using Microsoft Excel 2007 and Statistica version 6.0, 2003. We summarized baseline and demographic characteristics using descriptive statistics. To assess correlations, we used the Spearman rho test. A two-tailed p < 0.05 was considered statistically significant. Research results. We adapted the PAS questionnaire to better quantify existing symptoms, and the resulting mean scores were compared between the two main groups (Table 1). Table 1. PAS questionnaire score table for prenatal patients (mean scores) Symptom name Group 1n =11 Controln = 10 р1 Bone pain 97, 6 ± 8,3 2,2 ± 0,4 <0,0001 Rapid fatigue 94.7 ± 7,2 6,2 ± 0,3 <0,0001 Mood lability 95, 3 ± 5,9 7,5± 0,6 <0,0001 Depression 90, 6 ± 6,3 5,3± 0,8 <0,0001 Stomach ache 92,4 ± 5,4 4,4 ± 0,6 <0,0001 Weakness 93, 4 ± 7, 5 3,3 ± 0,4 <0,0001 Irritability 88,3 ± 6,2 3,4 ± 0,8 <0,0001 Joint pain 93,4 ± 5,8 3,1 ± 0,3 <0,0001 Forgetfulness 91,4 ± 6,9 4,8 ± 0,9 <0,0001 Difficulty rising from a sitting position 92,9± 7,8 2,5 ± 0,4 <0,0001 Headaches 90,8 ± 7,7 3,4 ± 0,8 <0,0001 Itchy skin 58,5 ± 6,3 1,9 ± 0,3 <0,0001 Thirst 69,8 ± 7,4 3,3 ± 0,6 <0,0001 Note: p - significance of differences between the study group and the control group. Table 1 shows that before delivery, the intensity of various symptoms as assessed by the PAS questionnaire was significantly higher in the study group compared to the control group. We then examined the characteristics of patient complaints by group (Table 2). Table 2: Characteristics of PHPT Patient Complaints in Comparisons, Absolute Number (n, %) Complaints Total n = 11 Main group n = 11 Control n = 10 Thirst 7 (63,4%)* 7 (63,4%)* - Polyuria 6 (54.5%) 6 (54.5%) - Weight loss 4 (36.4%) 4 (36.4%) - Brittle nails 8 (72,7%)* 8 (72,7%)* - Hair loss 10 (90,9%)** 10 (90,9%)** - SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 220 Note: * - reliability of differences between groups – main and control, where * is p < 0.05. As shown in Table 2, patients in the study group had complaints typical of PHPT, such as brittle nails (8 cases (72.7%)*), loosening and tooth loss (4 cases (36.4%)), "duck gait" (6 cases (54.5%)), decreased height (2 cases (9.09%), pathological bone fractures (2 cases (18.2%)), and renal colic attacks (1 case (9.09%) among 11 patients). It is commonly accepted that general description of the biochemical and hormonal parameters of patients with PHPT is given in Table 3. As can be seen from Table 3, there were significant differences in biochemical and hormonal parameters in patients with PHPT compared to the control group. Thus, PTH levels were significantly elevated in patients with PHPT (p < 0.0001). Mean vitamin D3 levels were significantly low in the PHPT study group (p < 0.05). Blood biochemistry parameters, including alkaline phosphatase, total calcium, and Ca++, were significantly high in the PHPT group (p < 0.05). Table 3 Hormonal and biochemical characteristics of patients in the study group, n = 11 Indicator Main group n =11 Control n = 10 Р Average age of patients, years (n=225) 30,2 ± 1,4 32,3 ± 3,5 >0,05 PTH level, pg/ml (n=225) 945,8±69,2*** 13,2 ± 2,1 <0,0001 Total calcium, mmol/l (n=225) 2,708±0,048* 2,2 ± 0,5 <0,05 25(OH)-D, pg/ml (n=166) 12,6 ± 3,3** 36,2 ± 8,5 <0,05 Phosphorus, mmol/l (n=225) 1,05 ± 0,2 1,23 ± 0,6 >0,05 Alkaline phosphatase, µm/l (n=225) 1513.8±213.7*** 67.5±9.4 < 0,05 Blood creatinine (n=225) (μmol/L) 69,8± 7,56* 111,12±4,18 <0,05 Ca++ mmol/L (n=225) 1.35±0.4* 0.91±0.02 <0,005 Note: p is the significance of differences between the study group and the control group, where * is p < 0.05, ** is p < 0.005, *** is p < 0.0001 Finally, we analyzed the parathyroid ultrasound results (Table 4). Table 4 Parathyroid ultrasound results in the study group N=11 PHPT Control Total Revealed 11 (100%) - 11 (100%) Not detected - - - Total 11(100%) - 11(100%) Duck walk 6 (54.5%) 6 (54.5%) - Pain in bones and joints 7 (63,4%)* 7 (63,4%)* - Pathological fractures 2 (18.2%) 2 (18.2%) - Decrease in growth 2 (18.2%) 2 (18.2%) - Loose teeth 4 (36.4%) 4 (36.4%) - Attacks of renal colic 1 (9.09%) 1 (9.09%) - Recurrent nephrolithiasis 2 (18.2%) 2 (18.2%) - SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 221 As shown in Table 4, ultrasound confirmed the presence of PHPT in all patients. Given the pregnancy, we deferred radioisotope scintigraphy until after delivery. It has been observed that despite existing guidelines, due to the rarity of PHPT and the lack of clinical experience, many aspects of the management of these patients require individualized consideration. Conclusions. 1. Primary hyperparathyroidism first detected during pregnancy poses a serious threat, as it can rapidly worsen and negatively impact the course of pregnancy. 2. Treatment of PHPT in pregnant women is limited in terms of both accurate diagnosis and drug therapy. If the condition progresses, surgery is recommended, preferably in the second trimester, when the fetal major organs are already formed and the risk of preterm delivery is reduced. 3. Careful monitoring of the mother and child is essential before surgery, and calcium levels in the newborn must be checked after delivery. REFERENCES 1. Asagoe T, Takami H, Hanatani Y, Kodaira S. [Parathyroid crisis]. Nihon Rinsho. 1995 Apr;53(4):925-9. Japanese. 2. Belyaeva AV, Rozhinskaya LY Treatment of hypercalcemia and hypercalcemic crisis // Intensive care. 2006. - Vol. 8. - No. 9. - Pp. 11-18. 3. Patterson R. Hyperparathyroidism in pregnancy /R.Patterson// Am. J Obstet. Gynecol.-1987.- P.70-457. 4. Clark, D. 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