Pseudohypoparathyroidism

Pseudohypoparathyroidism type 1A (PHP1A) is a disorder that causes many endocrine and developmental problems. To date, medical treatment has focused primarily on maintenance of normal serum levels of calcium, phosphorous, and thyroid hormone. However, these therapeutic interventions do not address the problems of short stature, obesity, and subcutaneous ossifications, which for many are a source of considerable morbidity and personal distress. These patients require frequent medical care, blood tests, and medication adjustments. PHP1A is an inherited condition with an estimated prevalence in the United States of 1:15,000- 20,000, and the studies that we propose provide an opportunity to improve the quality of life in affected patients. We have found that growth hormone (GH) deficiency is common in these patients, and our data suggest that GH testing should be part of their routine standard of care. We are investigating whether GH treatment can increase final adult height. We are also investigating whether GH treatment can reduce weight and improve a variety of metabolic disturbances and overall health in both children and adults. GH deficiency not only leads to short stature and obesity, but also to osteoporosis, hyperlipidemia, depressed cardiac and renal function, as well as an overall lack of energy. It is quite possible that treatment of GH-deficient patients with PHP1A could improve any or all of the above problems. GH treatment has been FDA approved for use in both children and adults with GH deficiency. Therefore, it may be possible to provide improvement in health and overall quality of life in these patients. Additionally, we completed a study in which we treated children with PHP1A who are not GH deficient (i.e., GH sufficient). The rationale is that GH treatment could maximize linear growth velocity prior to the premature bone fusion that occurs in this condition and potentially improve final adult height. The supply of growth hormone has ended for this study, and we are following those participants who were in this study and received the growth hormone supply. Some of these patients remain on growth hormone as per clinical care secondary to their responses. This study also seeks to define the specific neurocognitive and psychosocial disabilities in individuals with AHO in order to develop therapies and improve quality of life. AHO includes two subtypes: pseudohypoparathyroidism type 1A (PHP1A) and pseudopseudohypoparathyroidism (PPHP).

Researchers are evaluating the effects of the drug theophylline in 100 participants diagnosed with Pseudohypoparathyroidism (PHP), including subtypes PHP Ia, PHP IB, and PHP 1C. This open-label Phase 4 intervention study explores the off-label use of theophylline, which is a non-specific phosphodiesterase inhibitor that increases levels of a signaling molecule called cAMP. Because PHP patients have resistance to hormones involving cAMP signaling, the study investigates whether theophylline can reduce this resistance and potentially influence bone maturation, brain function, and metabolism. Participants will receive theophylline with doses adjusted to maintain peak blood levels between 10 and 15 micrograms per milliliter. The treatment details focus on monitoring and maintaining these therapeutic drug levels throughout the study period. No additional comparator groups or placebo treatments are mentioned. During the study, participants will be closely monitored for the effect of theophylline on bone age over a 52-week period. Various assessments related to bone growth and overall health are conducted to evaluate the drug's impact. Safety monitoring will also include observing for any adverse effects or interactions, especially given the specific health exclusions. The total participation duration involves regular follow-ups across the one-year study timeline to track outcomes and ensure participant well-being.

Patients with rare and complex genetic syndromes often face multiple medical problems affecting various organs and frequently have intellectual disabilities. While these patients receive specialized multidisciplinary care during childhood, improved medical care has extended their life expectancy, allowing more to reach adulthood. However, adult medical care for these patients is often fragmented and lacks coordinated multidisciplinary follow-up, highlighting the urgent need for comprehensive adult care guidelines and an overview of their medical needs. This research involves a retrospective file study analyzing medical histories, laboratory results, additional tests, and records of physical and psychological complaints for adults with rare genetic syndromes. The study focuses on understanding their comorbidities, medication use, and how medication doses may need adjustment according to each syndrome. No new treatments are given; instead, existing medical data will be reviewed using statistical software. Participants' past medical records will be examined to assess physical health problems, laboratory values, psychological and physical complaints, and medication use over one year. The goal is to generate an overview of medical needs and quality of life impacts in this population. Data analysis will be performed retrospectively without requiring additional procedures from participants.

Researchers are studying imprinting disorders (IDs), which affect both children and adults, to better understand their natural progression and how these disorders impact metabolism. The study focuses on patients with confirmed molecular diagnoses of IDs, examining a variety of conditions including Silver Russell Syndrome, Beckwith-Wiedemann Syndrome, and Prader-Willi Syndrome among others. The goal is to explore common metabolic profiles, risks, and potential therapeutic approaches related to these disorders. This observational study involves following patients who have signed informed consent, including adults and children, regardless of the severity of their condition. Researchers aim to identify common metabolic patterns and assess how different imprinting disorders influence metabolic characteristics. The study does not involve any treatment interventions but focuses on detailed molecular and metabolic profiling. Participants will be monitored over an average of 10 years to gather comprehensive clinical, genetic, biological, and morphometric data. The study evaluates the natural history of IDs through this long-term observation, collecting information that may help classify and predict outcomes for these disorders. This extended follow-up will contribute to understanding the metabolic consequences and support the development of common therapeutic strategies.

Researchers are creating and managing a national Italian database to study patients with hypoparathyroidism or pseudohypoparathyroidism, two rare diseases affecting parathyroid function and calcium balance. The study aims to collect detailed medical, genetic, clinical, and treatment data from a wide group of patients across Italy to better understand these conditions, their prevalence, and incidence. This research will help improve knowledge about different forms of these diseases and support optimal care planning. The study involves 41 specialist centers throughout Italy, including endocrinology and pediatric departments, where patients with these conditions are treated. Data will be gathered both retrospectively from medical records at the time of recruitment and prospectively during follow-up visits over a 10-year period. No new treatments or interventions are administered by the study; instead, information on patients' usual treatments and responses will be collected. Participants will have their medical histories, clinical features, bone health, laboratory results, and quality of life monitored regularly as part of their usual care. The study will assess disease characteristics, bone fragility, and treatment responses over time, aiming for long-term analysis up to 10 years. Data will be collected anonymously and analyzed to improve understanding and management of these rare diseases.

Parathyroid disorders, which involve problems with parathyroid hormone regulation affecting calcium and phosphate balance, are common and can include excess, deficiency, or hormone signaling defects. This research aims to investigate the causes of these disorders, including genetic factors, and to describe their natural history, progression, and related syndromic conditions such as multiple endocrine neoplasia and hyperparathyroidism-jaw tumor syndrome. The study also seeks to understand associated manifestations like tumors and to explore long-term risks and benefits of standard treatments. Participants with confirmed, suspected, or at-risk parathyroid disorders will receive standard care testing and treatment, which may be provided in person or through telehealth. The study involves collecting biological samples such as saliva, blood, urine, stool, cheek cells, and possibly skin biopsies from adults. Medical photos may be taken, and leftover tissue from surgeries may be collected for research. Participants will continue in the study as long as they receive care from their doctors. Throughout the study, participants will undergo medical record reviews, testing, questionnaires about physical, mental, and social health, and sample donations. Researchers will analyze these data to identify disease biomarkers and molecular profiles over a five-year period. The study will also investigate causes, disease mechanisms, and progression, including during pregnancy, while monitoring morbidity, mortality, and associated conditions. Participation duration depends on ongoing clinical care.

Researchers are evaluating the potential added benefits of using a near-infrared autofluorescence probe-based imaging system called PTeye to identify parathyroid glands during thyroid surgery compared to the surgeon's visual identification without PTeye. This trial focuses on patients undergoing first-time total thyroidectomy and aims to see if PTeye improves the number of parathyroid glands identified and preserved, reduces postoperative hypoparathyroidism, and decreases the need for calcium and vitamin D treatment after surgery. The study randomly assigns patients into two groups: one where the PTeye device is used during surgery to detect parathyroid glands by measuring autofluorescence signals, and a control group where surgeons identify glands using only their naked eyes. During surgery in the PTeye group, the surgeon takes baseline measurements on the thyroid or neck muscle, then uses a sterile fiber optic probe to identify parathyroid tissue. If parathyroid glands are accidentally removed, they are reimplanted in the neck muscle according to standard procedures in both groups. Participants will have their demographic data, surgery duration, frozen section analyses, histology reports, blood calcium and parathyroid hormone levels monitored before and after surgery, along with any calcium or vitamin D supplementation and complications. These measurements will be compared between the PTeye and control groups to assess the device's impact. Outcome measures include the number of parathyroid glands identified during surgery, postoperative hormone levels, and incidence of hypoparathyroidism, with follow-up extending up to six months post-surgery.

Turner syndrome is a condition in girls characterized by the absence or partial absence of one of the two X chromosomes, leading to short stature due to a gene deficiency affecting growth. This Phase 2 study evaluates the use of vosoritide, a medication that targets growth plate cells to help increase height, in pre-pubertal girls with Turner syndrome who either have not previously used growth hormone or have shown poor response to it. The goal is to assess whether vosoritide can improve growth velocity in these patients. Participants will receive vosoritide through daily injections under the skin for 12 months, using doses based on weight as approved for a related condition. Those who respond positively during this period may continue treatment in an extension phase until their growth stops. Vosoritide treatment is the only intervention during the study, replacing or supplementing prior growth hormone therapy if applicable. Throughout the study, participants will be closely monitored for safety and growth progress. Researchers will track adverse events and measure changes in growth speed and height standardized for age and sex over 12 months. The study uses patients' historical growth data from the previous 6 to 18 months to compare outcomes. Regular assessments include height measurements and health monitoring to evaluate vosoritide's effects and safety over the course of participation.