Continuous subcutaneous rhPTH infusion for managing difficult chronic hypoparathyroidism. A systematic review.

PURPOSE: Standard treatment for chronic hypoparathyroidism is represented by long-life per os supplementation of calcium and vitamin D. Since 90s, exogenous PTH is also available, but a not negligible number of patients experience a poor control. Starting from the experience with pumps in diabetes, it has been hypothesized that the infusion of PTH through pump might result in a better disease control. The aim of this systematic review is to summarize the published data about continuous subcutaneous PTH infusion in chronic hypoPTH patients and achieve conclusions for clinical practice. METHODS: A comprehensive computer literature search of the PubMed/MEDLINE, Embase, and Scopus databases was conducted by two authors independently (last search on November 30, 2022). All findings were summarized and critically discussed. RESULTS: We included 14 of the 103 retrieved articles, 2 RCTs, 8 case reports, and 4 case series, published between 2008 and 2022. Of the total 40 patients, 17 were adults, and 23 pediatric. The etiology was postsurgical in 50% of cases and genetic in the other 50%. All had a failure of standard care and a rapid improvement of clinical and biochemical parameters on PTH pump therapy, without severe adverse events. CONCLUSIONS: Based on literature, pump PTH infusion may represent an effective, safe, and feasible option for patients with chronic hypoparathyroidism refractory to standard therapy. From a clinical perspective, careful patient selection, a skilled healthcare team, the assessment of the local setting and the collaboration with pump suppliers are essential.

Combining topical dermal infused exosomes with injected calcium hydroxylapatite for enhanced tissue biostimulation.

BACKGROUND: Exosome research continues to flourish. Subsequent knowledge surrounding indications, dose-response, safety, efficacy, and the ability to combine exosome treatment as a "skin primer"-for biostimulation modalities such as calcium hydroxylapatite (CaHA), platelet-rich plasma (PRP), and platelet-rich fibrin matrix (PRFM) is growing rapidly. The objective of this study was to develop safe, reproducible methods of improving topical exosome absorption to enhance the quality of skin either by themselves, or in combination with injectable CaHA. METHODS: Under IRB Approval (International Cell Surgical Society: ICSS-2022-007), 40 patients were enrolled in this study. Twenty patients underwent facial biostimulatory dermal infusion alone, to determine if this method allowed adequate exosome absorption. Five patients underwent facial biostimulatory infusion followed immediately by Dilute CaHA injection (1:1 dilution) to the face. Five patients underwent exosome biostimulatory dermal infusion followed immediately by hyperdilute CaHA (dilution 1:4) injection to the neck. Five patients underwent Facial Dilute CaHA injection (1:1 dilution) alone, without dermal infusion. Five patients underwent neck hyperdilute CaHA injection (1:4 dilution) alone, without dermal infusion. All patients had pretreatment Quantificare 3-D photo-documentation and skin analysis (Quantificare, France). In all patients, the skin was first cleansed with a gentle glycolic acid facial wash (Gregory MD). To induce a "homing inflammatory environment" for the exosomes, sea salt exfoliation was performed (SaltFacial®, SaltMed, Cardiff, CA). A nitric oxide-generating serum (N101 Pneuma Nitric Oxide, Austin, TX) was then applied to act as an enhanced vehicle for absorption. A 3 MHz ultrasound (SaltFacial®, SaltMed, Cardiff, CA) was then utilized to further deepen the absorption of the nitric oxide serum. A topical emulsion containing equal volumes (1.0 cc containing 1 million) of exosomes (Kimera Labs, Miramar, FL), 25 units of botulinum toxin (Xeomin, Merz Aesthetics, Raleigh, NC) and hyaluronic acid (Belatero, Merz Aesthetics, Raleigh, NC) was mixed via back-and-forth propulsion in a 3-cc syringe. When adequately mixed, the emulsion was then applied to the treatment areas. The cavitating ultrasound was then used to aid in the absorption of the emulsion. The patients were then treated with high-intensity LED therapy (SaltFacial®, SaltMed, Cardiff, CA), utilizing the collagen restoration preset program of combination red (660 nm) near-infrared (930 nm) wavelength for 20 min. Post-treatment Quantificare analysis was performed at 15 and 30 days after treatment. RESULTS: Without exception, all dermal infusion alone and CaHA injection alone patients showed an improvement in the tone, quality, and texture of their skin. Quantificare results showed consistent improvement in wrinkles, pores, skin evenness, improved vascularity, and a reduction in oiliness and unwanted pigment. When employed as a skin primer prior to injections (CaHA), enhanced and more rapid results were seen. CONCLUSIONS: Biostimulatory dermal infusion can be achieved utilizing topical placental mesenchymal stem cell-derived exosomes. These exosomes can be used alone, or mixed with ancillary ingredients such as botulinum toxin, hyaluronic acid dermal filler, and CaHA to customize and personalize treatments based upon individual patient needs. Topical absorption is enhanced with sea salt exfoliation, a topical nitric oxide-generating serum, and 3 MHz cavitating ultrasound. Post-absorption activity is enhanced with high-intensity LED treatment. The addition of CaHA injections after the topical exosome "priming of the skin" yielded enhanced skin quality faster than exosomes or CaHA alone.

Alteration of lung tissues proteins in birch pollen induced asthma mice before and after SCIT.

Subcutaneous immunotherapy (SCIT) is a classic form of allergen-specific immunotherapy that is used to treat birch pollen induced allergic asthma. To investigate the underlying molecular mechanisms of SCIT, we aimed to profile lung samples to explore changes in the differential proteome before and after SCIT in mice with allergic asthma. Fresh lungs were collected from three groups of female BALB/c mice: 1) control mice, 2) birch pollen-induced allergic mice, and 3) birch pollen-induced allergic mice with SCIT. Tandem mass tag (TMT) labelling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze the lung proteome in the mice. Ingenuity pathway analysis (IPA) and Gene Ontology (GO) classification analysis were applied to identify differentially expressed proteins (DEPs) and crucial pathways. The screened DEPs were validated by immunohistochemistry analysis. A total of 317 proteins were upregulated and 184 proteins were downregulated in the asthma group compared to those of the control group. In contrast, 639 DEPs (163 upregulated and 456 downregulated proteins) were identified after SCIT in comparison with those of the asthma group. Among the 639 DEPs, 277 proteins returned to similar levels as those of the relative non-asthma condition. Bioinformatic analysis revealed that the 277 proteins played a significant role in the leukocyte extravasation signaling pathway. The leukocyte extravasation signaling pathway and related DEPs were of crucial importance in birch pollen SCIT.

Treatment of subcutaneous nodules after infusion of apomorphine; a biopsy-controlled study comparing 4 frequently used therapies.

This study aimed to provide clinical evidence for existing treatments of subcutaneous nodules after subcutaneous infusion of apomorphine, using a biopsy-controlled prospective crossover design of four treatments. We demonstrated that dilution of apomorphine significantly improved patient satisfaction, while subcutaneous hydrocortisone reduced nodule size, however with no differences in the histopathology.

Regulation of Rhcg, an ammonia transporter, by aldosterone in the kidney.

Rhesus C glycoprotein (Rhcg), an ammonia transporter, is a key molecule in urinary acid excretion and is expressed mainly in the intercalated cells (ICs) of the renal collecting duct. In the present study we investigated the role of aldosterone in the regulation of Rhcg expression. In in vivo experiments using C57BL/6J mice, Western blot analysis showed that continuous subcutaneous administration of aldosterone increased the expression of Rhcg in membrane fraction of the kidney. Supplementation of potassium inhibited the effect of aldosterone on the Rhcg. Next, mice were subjected to adrenalectomy with or without administration of aldosterone, and then ad libitum 0.14 M NH4Cl containing water was given. NH4Cl load increased the expression of Rhcg in membrane fraction. Adrenalectomy decreased NH4Cl-induced Rhcg expression, which was restored by administration of aldosterone. Immunohistochemical studies revealed that NH4Cl load induced the localization of Rhcg at the apical membrane of ICs in the outer medullary collecting duct. Adrenalectomy decreased NH4Cl-induced membrane localization of Rhcg, which was restored by administration of aldosterone. For in vitro experiments, IN-IC cells, an immortalized cell line stably expressing Flag-tagged Rhcg (Rhcg-Flag), were used. Western blot analysis showed that aldosterone increased the expression of Rhcg-Flag in membrane fraction, while the increase in extracellular potassium level inhibited the effect of aldosterone. Both spironolactone and GÓ§6983, a PKC inhibitor, inhibited the expression of Rhcg-Flag in the membrane fraction. These results suggest that aldosterone regulates the membrane expression of Rhcg through the mineralocorticoid receptor and PKC pathways, which is modulated by extracellular potassium level.

Efficacy of N-acetylcysteine in the prevention of alcohol relapse-like drinking: Study in long-term ethanol-experienced male rats.

Alcohol use disorders are chronic and highly relapsing disorders, thus alcoholic patients have a high rate of recidivism for drug use even after long periods of abstinence. The literature points to the potential usefulness of N-acetylcysteine (NAC) in the management of several substance use disorders probably due to its capacity to restore brain homeostasis of the glutamate system disrupted in addiction. However, there is little evidence in the case of alcohol. The aim of this study was to explore the potential anti-relapse efficacy of NAC using the alcohol deprivation effect (ADE) model in long-term experienced rats. Two experiments were performed in male Wistar rats to: (a) test the efficacy of NAC to prevent relapse and (b) discriminate the best administration schedule (intermittent vs. continuous) for NAC. In the first experiment, animals were implanted with mini-osmotic pumps delivering 0 or 1 mg/hr NAC during 14 days. In a second experiment, rats received 0, 60, or 100 mg/kg once daily by subcutaneous injection. The efficacy to prevent ADE was evaluated in both experiments. NAC subcutaneously administered, either by continuous infusion or by intermittent injections regimen, is able to block the ADE. The best results were obtained after using 60 mg/kg NAC dose. Our findings support the hypothesis that NAC may represent a valuable therapy in the management of alcohol relapse.

Physiologically Based Pharmacokinetics of Dexamethasone in Rats.

Blood and multitissue concentration-time profiles for dexamethasone (DEX), a synthetic corticosteroid, were measured in male rats after subcutaneous bolus and infusion dosing. A physiologically based pharmacokinetics (PBPK) model was applied for 12 measured tissues. Tissue partition coefficients (K p ) and metabolic clearance were assessed from infusion studies. Blood cell to plasma partitioning (0.664) and plasma free fraction (0.175) for DEX were found to be moderate. DEX was extensively partitioned into liver (K p = 6.76), whereas the calculated K p values of most tissues ranged between 0.1 and 1.5. Despite the moderate lipophilicity of DEX (log P = 1.8), adipose exhibited very limited distribution (K p = 0.17). Presumably due to P-glycoprotein-mediated efflux, DEX concentrations were very low in brain compared with its expected high permeability. Infusion studies yielded K p values from male and female rats at steady state that were similar. In silico K p values calculated for different tissues by using GastroPlus software were similar to in vivo values except for adipose and liver. Glucocorticoid receptors are found in diverse tissues, and these PBPK modeling results may help provide exposure profiles driving pharmacodynamic effects of DEX. SIGNIFICANCE STATEMENT: Our physiologically based pharmacokinetics model describes the experimentally determined tissue and plasma dexamethasone (DEX) pharmacokinetics (PK) profiles in rats reasonably well. This model can serve for further investigation of DEX tissue distribution in rats as the PK driving force for PD effects in different tissues. No major sex differences were found for DEX tissue distribution. Knowledge gained in this study may be translatable to higher-order species including humans.

Clinical Practice Experience with HyQvia in Adults Using Alternative Dosing Regimens and Pediatric Patients: A Retrospective Study.

INTRODUCTION: HyQvia (Immune Globulin Infusion 10% [Human] with Recombinant Human Hyaluronidase) was developed to combine the advantages of intravenous and subcutaneous immune globulin (SCIG), allowing administration of larger volumes at a single subcutaneous site with less frequent dosing when compared to other SCIG products. Current US prescribing guidelines for HyQvia are limited to adults and do not encompass the flexibility required to achieve success in all patients with primary immunodeficiency (PID). METHODS: This retrospective study was designed to evaluate the clinical experience of treating patients with PID with HyQvia regimens outside of package insert recommendations as well as in pediatric patients. Data were abstracted from 38 patient records (317 HyQvia infusions), including five patients less than 16 years of age, from seven US immunology clinics. RESULTS: Among 37 patients receiving HyQvia regimens differing from prescribing guidelines, the most notable variations included shorter ramp-up periods, use of two rather than one infusion site, and slower than maximal infusion rates to mitigate local adverse events (AEs). The medication volume infused for single site doses ranged from 75 to 200 mL and doses split between two sites ranged from 100 to 750 mL. The most common type of regimen variation was a condensed ramp-up phase (shorter schedule, higher doses), and 96% (24/25) of patients managed in this way completed ramp-up. The most common ramp-up schedule was three infusions (one at 25-45%, another at 50-75%, and the final at 100% of target dose) spread over 2-4 weeks. CONCLUSIONS: A shorter ramp-up schedule did not appear to increase the number of AEs compared to standard ramp-up schedules. For patients with AEs, slower infusion rates and the use of two sites may improve medication tolerability. Four of five pediatric patients reported no AEs, and only one discontinued, stating a fear of needles. HyQvia may be tailored to adults requiring alternative rates, ramp-up, and/or dosing regimens and may be especially well-suited to children.

Subcutaneous maternal resveratrol treatment increases uterine artery blood flow in the pregnant ewe and increases fetal but not cardiac growth.

KEY POINTS: Substrate restriction during critical developmental windows of gestation programmes offspring for a predisposition towards cardiovascular disease in adult life. This study aimed to determine the effect of maternal resveratrol (RSV) treatment in an animal model in which chronic fetal catheterisation is possible and the timing of organ maturation reflects that of the human. Maternal RSV treatment increased uterine artery blood flow, fetal oxygenation and fetal weight. RSV was not detectable in the fetal circulation, indicating that it may not cross the sheep placenta. This study highlights RSV as a possible intervention to restore fetal substrate supply in pregnancies affected by placental insufficiency. ABSTRACT: Suboptimal in utero environments with reduced substrate supply during critical developmental windows of gestation predispose offspring to non-communicable diseases such as cardiovascular disease (CVD). Improving fetal substrate supply in these pregnancies may ameliorate the predisposition these offspring have toward adult-onset CVD. This study aimed to determine the effect of maternal resveratrol (RSV) supplementation on uterine artery blood flow and the direct effects of RSV on the fetal heart in a chronically catheterised sheep model of human pregnancy. Maternal RSV treatment significantly increased uterine artery blood flow as measured by phase contrast magnetic resonance imaging, mean gestational fetal PaO2 and SaO2 as well as fetal weight. RSV was not detectable in the fetal circulation, and mRNA and protein expression of the histone/protein deacetylase SIRT1 did not differ between treatment groups. No effect of maternal RSV supplementation on AKT/mTOR or CAMKII signalling in the fetal left ventricle was observed. Maternal RSV supplementation is capable of increasing fetal oxygenation and growth in an animal model in which cardiac development parallels that of the human.

Tolerability and surrogate efficacy parameters of a polymerized depot mixture pollen extracts without dilutional effect.

Aim: To evaluate tolerability of subcutaneous immunotherapy, in a polymerized mixture (Olea europaea/Phleum pratense) depot presentation. Patients & methods: A total of 47 poly-allergic patients received: an abbreviated schedule with three injections at weekly intervals or a cluster schedule with two administrations in 1 day. Both treatments continued with 3 monthly maintenance administrations. Results: Two systemic reactions, (4.3%). One grade 0 and one grade I. No local reactions. Immunoglobulin levels, increased significantly at final visit versus baseline in sIgG and sIgG4; in both schedules and allergens, no significant changes in specific immunoglobulin E levels were detected. Cutaneous reactivity at final visit decreased significantly. Conclusion: Both administration schedules with polymerized mixture of O. europaea/P. pratense, presented an excellent tolerability profile and induced preliminary efficacy changes.

Tolerability and positive efficacy results after subcutaneous immunotherapy with Parietaria judaica depot extract.

AIM: To evaluate tolerability and efficacy of Parietaria judaica subcutaneous immunotherapy on patients with allergic rhinoconjunctivitis. PATIENTS & METHODS: 51 patients were assigned to build-up scheme (six increasing doses) of P. judaica depot native extract, plus three maintenance monthly administrations. RESULTS: Out of 470 administered doses, only 3.8% elicited systemic reactions (1.5% nonspecific and 2.3% grade I). Concerning the exploratory efficacy parameters: cutaneous reactivity at the final visit versus baseline was significantly decreased; specific titers of IgG and IgG4 increased significantly and patients showed a significant decrease in the rhinitis symptoms score. CONCLUSION: P. judaica subcutaneous immunotherapy (Allergovac® depot ROXALL Medicina España S.A., Zamudio, Spain) with an abbreviated up-dosing scheme showed an adequate safety and tolerability profile and induced preliminary efficacy changes.

Pattern dystrophies in patients treated with deferoxamine: report of two cases and review of the literature.

BACKGROUND: Deferoxamine (DFO) is one of the most commonly used chelation treatments for transfusional hemosiderosis. Pattern dystrophies constitute a distinct entity of retinal disorders that has been occasionally identified in association with deferoxamine. CASE PRESENTATION: We report two cases of bilateral macular pattern dystrophy in transfusion dependent patients undergoing chronic chelation therapy with deferoxamine due to thalassemias. Our patients were evaluated with multimodal imaging and the results are presented. Both patients had normal cone and rod responses in the full-field electroretinogram and continued the prescribed chelation therapy, after hematology consult. The patients were followed up every 3 months for 2 and 4 years respectively for possible deterioration. Their best corrected visual acuity remained stable with no anatomic change on Optical Coherence Tomography findings. CONCLUSION: Multimodal imaging of our patients allowed a better evaluation and possibly earlier detection of the DFO-related changes. Screening and close follow up of patients under chronic chelating therapy is important in order to promptly diagnose and manage possible toxicity either with discontinuation of the offending agent or dose modification.

Rapid Push vs Pump-Infused Subcutaneous Immunoglobulin Treatment: a Randomized Crossover Study of Quality of Life in Primary Immunodeficiency Patients.

PURPOSE: Subcutaneous immunoglobulin replacement therapy (IgRT) may be administered once a week with a pump or every other day with a syringe (rapid push). The objective of the study was to compare the impact of pump and rapid push infusions on patient's life quality index (LQI). METHODS: This study was a randomized, crossover, multicenter, non-inferiority trial conducted in adults with primary immunodeficiency (PID) accustomed to weekly infusions at home by pump. Patients used pump or rapid push for 3 months each according to the randomized sequence. Main criterion was PID-LQI factor I (treatment interference). Non-inferiority ratio was set at 90%. RESULTS: Thirty patients entered the study; 28 completed the two periods. IgRT exposure was similar during each period. At the end of each period, mean LQI factor 1 was 87.0 (IC95% [80.3; 94.3]) and 77.80 (IC95% [71.5; 84.7]) for pump and rapid push, respectively. There was a slightly larger effect of rapid push on treatment interference than with pump so that the primary endpoint could not be met. No difference was found on other LQI components, satisfaction (TSQM), or quality of life (SF36v2). Eight patients declared to prefer rapid push while 19 others preferred pump. Of rapid push infusions, 67.2% led to local reactions vs 71.8% of pump infusions (p = 0.11) illustrating its good tolerance. Rapid push and pump infusions achieved similar trough IgG levels with similar incidence of infections. Rapid push saved 70% of administration cost when compared to pump. CONCLUSIONS: Since IgRT is a lifelong treatment in PID patients, individualization of treatment is of paramount importance. Rapid push is a new administration method in the physician's armamentarium which is preferred by some patients and is cost-effective. CLINICALTRIALS. GOV IDENTIFIER: NCT02180763 CLINICAL IMPLICATIONS: Self-administration of small volumes of immunoglobulins at home, every other day, using a syringe (rapid push) is a cost-effective alternative to administration of larger volumes by pump once a week. This study compared subcutaneous infusions of immunoglobulins either weekly via a pump or every other day via a syringe (rapid push). Rapid push is preferred by some patients and is cost-effective, therefore completing a physician's armamentarium.

Subcutaneous local anesthetic infusion could eliminate use of epidural analgesia after the Nuss procedure.

AIM: To compare outcomes of continuous subcutaneous infusion of local anesthetic and epidural analgesia following the Nuss procedure. PATIENTS & METHODS: A retrospective chart review compared patients managed with subcutaneous local anesthetic infusion (n = 12) versus thoracic epidural (n = 19) following the Nuss procedure from March 2013 to June 2015. RESULTS: There was no difference in hospital length of stay or days on intravenous narcotics. Epidural catheter placement prolonged operating room time (146.58 ± 28.30 vs 121.42 ± 21.98 min, p = 0.01). Average pain scores were slightly higher in the subcutaneous infusion group (3.72 ± 1.62 vs 2.35 ± 0.95, p = 0.02), but of negligible clinical significance. CONCLUSION: Continuous subcutaneous infusion of local anesthetic could eliminate the need for thoracic epidural for pain management after the Nuss procedure.

Ninety-day Local Tolerability and Toxicity Study of ND0612, a Novel Formulation of Levodopa/Carbidopa, Administered by Subcutaneous Continuous Infusion in Minipigs.

A 90-day study in Göttingen minipigs was conducted to test the local tolerability and systemic toxicity of ND0612, a novel aqueous solution of carbidopa (CD)/levodopa (LD) intended for the treatment of Parkinson's disease by continuous subcutaneous administration using a discrete infusion pump. To evaluate tissue site reactions, we used a unique study design involving multiple infusion sites to evaluate the effect of dose per site (270/63, 360/45, and 360/84 mg LD/CD), volume of infusion per site (4.5 and 6 ml per site), formulation concentration (60/14 and 60/7.5 mg/ml LD/CD), daily rate of infusion per site (240 µl/hr for16 hr and 80 µl/hr for 8 hr, 320 µl/hr for 16 hr and 100 µl/hr for 8 hr, or 750 µl/hr for 8 hr), frequency (once every 5, 10, 15, or 20 days), and number of infusions (4, 6, or 9) to the same infusion site. No systemic adverse effects were observed. Histopathological changes at infusion sites started with localized minimal necrosis and acute inflammation that progressed to subacute and chronic inflammatory and reparative changes with evidence of progressive recovery following the final infusion. None of the infusion site effects were judged to be adverse, and clinical exposures to ND0612 are not expected to result in adverse responses.

Tumescent anaesthesia: its applications and well tolerated use in the out-of-operating room setting.

PURPOSE OF REVIEW: Tumescent anaesthesia is a method of administering dilute local anaesthetic into the subcutaneous tissue. Many anaesthesiologists are unfamiliar with the technique, its applications and potential risks. RECENT FINDINGS: The maximum safe dose of lidocaine with epinephrine in tumescent anaesthesia for liposuction is probably between 35 and 55 mg/kg. Without liposuction, the maximum dose of lidocaine with epinephrine should be no more than 28 mg/kg. After tumescent infiltration for liposuction, serum lidocaine concentrations peak between 12 and 16 h after injection. When tumescent lidocaine without epinephrine is used for endovenous laser therapy, peak serum lidocaine concentrations are observed much earlier, between 1 and 2 h after injection. Slow administration of more dilute concentrations of local anaesthetic decreases the risk of local anaesthetic systemic toxicity. SUMMARY: Although appealing because of its ability to provide prolonged analgesia, high doses of local anaesthetic are frequently administered using the tumescent technique, and absorption of local anaesthetic from the subcutaneous tissue is variable. When caring for patients having procedures in which tumescent anaesthesia is used, the risk of local anaesthetic toxicity should be acknowledged and lipid emulsion should be available for prompt treatment if needed.

Pulsatile GnRH Therapy May Restore Hypothalamus-Pituitary-Testis Axis Function in Patients With Congenital Combined Pituitary Hormone Deficiency: A Prospective, Self-Controlled Trial.

Context: The effectiveness of pulsatile gonadotropin-releasing hormone (GnRH) therapy in patients with congenital combined pituitary hormone deficiency (CCPHD) has not been investigated because of the limited number of patients, as well as these patients' presumed pituitary hypoplasia, poor gonadotrophic cell reserve, and impaired gonadotrophic response to GnRH. Objective: To assess the pituitary response to pulsatile GnRH therapy in men with CCPHD. Design: Prospective, self-controlled, 3-month clinical trial. Settings: University endocrine clinic. Patients: Men with hypogonadotropic hypogonadism caused by CCPHD. Intervention: Pulsatile GnRH was administered subcutaneously for 3 months. Main outcome measures: Primary endpoints were total serum testosterone, testicular volume, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Secondary endpoints included occurrence of spermatogenesis. Results: A total of 40 men with CCPHD completed the study. Of these, 60% (24 of 40) showed a good response to pulsatile GnRH treatment (response group). At 3 months, their LH and FSH levels increased to within the normal range and their testosterone levels increased to 8.67 ± 4.83 nmol/L. Of the patients in the response group, 33.3% (8 of 24) of them achieved spermatogenesis. The remaining 40% (16 of 40) of patients had a poor response to pulsatile GnRH treatment. Magnetic resonance imaging (MRI) did not reveal any correlation between pituitary response and pituitary height and/or integrity of the pituitary stalk. Conclusions: This study suggests that gonadotrophs in patients with CCPHD can exist and be functional-even with MRI evidence of pituitary hypoplasia or dysplasia. Pulsatile GnRH therapy restored pituitary-testis axis function in 60% of patients with CCPHD. These results may directly guide the clinical therapeutic choice.