Calcium is an essential element for normal physiologic function. Normal serum calcium is maintained within a close range of 8.4 to 10.4 mg/dL, and acute or severe changes can result in serious cardiac, musculoskeletal, and neurologic consequences. Normal calcium levels are maintained by interactions of parathyroid hormone and vitamin D. Parathyroid hormone regulates calcium levels via bone resorption, renal calcium reabsorption, and enhanced calcium absorption in the small intestine. Causes of hypocalcemia include hypoparathyroidism (often postsurgical), severe chronic kidney disease, and vitamin D deficiency. Laboratory testing for serum parathyroid hormone, kidney function, vitamin D metabolites, and serum phosphorus can help differentiate among causes. Acutely symptomatic patients require inpatient treatment with intravenous calcium gluconate, cardiac monitoring, and correction of hypomagnesemia. Hypercalcemia is most often due to primary hyperparathyroidism or malignancy. In the evaluation, hypercalcemia should first be confirmed by measurement of ionized calcium or repeat measurement of total serum calcium and correction for albumin. Obtaining a serum parathyroid hormone level is the next step. Asymptomatic, chronic mild hypercalcemia is often caused by primary hyperparathyroidism, which can be observed or treated surgically. Patients with severe hypercalcemia may have profound dehydration and require inpatient treatment with intravenous fluids, bisphosphonates, and calcitonin.
Prostate cancer is the second most common cancer in US men. Guidelines for screening vary, underscoring the need to engage patients in shared decision-making and counsel them about potential benefits and harms. When screening is undertaken, it is based on the prostate-specific antigen test, with digital rectal examination used selectively as an adjunct. Men with an abnormal prostate-specific antigen level should have a repeat test within a few months, before proceeding to biomarker testing, referral to urology, biopsy, and potentially imaging. Patients with newly diagnosed prostate cancer should be risk-stratified using clinical tumor (T) stage as determined by digital rectal examination, International Society of Urological Pathology grade group (Gleason score), prostate-specific antigen level, and tumor volume on biopsy. Treatment options vary by risk. Active surveillance is recommended for patients with low-risk disease, typically those with grade group 1/Gleason score of 6 (3 + 3). For patients with favorable intermediate-risk prostate cancer, treatment options are active surveillance, radiation therapy, or radical prostatectomy. For patients with unfavorable intermediate- or high-risk prostate cancer and estimated life expectancy greater than 10 years, options are radical prostatectomy or radiation therapy plus androgen deprivation therapy. For patients with prostate-specific antigen levels greater than 40 ng/dL, a Gleason score of 9 or higher, or locally advanced prostate cancer, treatment with radiation therapy and androgen deprivation therapy can additionally include concurrent abiraterone plus prednisone for 2 years. Focal ablation is also an option for some patients. Prognosis varies by disease features; men with low-risk prostate cancer are much more likely to die from other causes, whereas those with distant metastases have a 5-year relative survival rate of 38.3%.
Chronic prostatitis/chronic pelvic pain syndrome is a common male genitourinary condition comprising urinary, musculoskeletal, gastrointestinal, and/or psychological concerns with pain as a prominent feature. It is a diagnosis of exclusion. Physicians should use validated patient questionnaires to inventory presenting symptoms and symptom evolution over time. Questionnaires, such as the National Institutes of Health Chronic Prostatitis Symptom Index, can be particularly helpful in monitoring treatment effect on symptoms. Standardized classification systems can prove useful in choosing therapeutic modalities. Treatment should be individualized for each patient and multimodal; it should focus on symptomatic improvement, with a 25% or 6-point reduction in the National Institutes of Health Chronic Prostatitis Symptom Index score being defined as success. Chronic prostatitis/chronic pelvic pain syndrome is a chronic pain condition. Although pharmacologic and nonpharmacologic treatment modalities have variable proven benefit, few are supported by robust evidence. Chronic prostatitis/chronic pelvic pain syndrome does not predispose men to prostate cancer, but it may be associated with male infertility. Physicians should also be alert for its mental health effects on men.
Lower urinary tract symptoms that significantly impair quality of life in men may result from benign prostatic hyperplasia, overactive bladder, or a combination of both conditions. The diagnosis of benign prostatic hyperplasia, a voiding dysfunction due to outlet obstruction, can be made with a thorough history and physical examination. A validated questionnaire should be used to make an accurate initial diagnosis and to monitor treatment effect over time. Selective alpha-1 blockers are an appropriate first-line drug choice for most patients; however, 5-alpha reductase inhibitors and phosphodiesterase type 5 inhibitors may also be used, alone or in combination with each other, depending on symptom severity and if alternative treatment options are needed. If medical therapy is ineffective, surgical and interventional procedures aimed at opening the prostatic urethra are available to ameliorate symptoms. Overactive bladder manifests with urinary urgency, frequency, and nocturia with or without incontinence. The diagnosis of this storage dysfunction due to detrusor overactivity can be made with a thorough history, physical examination, urinalysis, and assessment of the residual volume of urine in the bladder after voiding. First-line treatment for overactive bladder includes beta-3 agonists as well as pelvic floor physical therapy and behavioral interventions. If left untreated, benign prostatic hyperplasia and overactive bladder can result in significant social isolation and relationship strain.
Although metabolic, viral, and drug- and alcohol-related etiologies are a familiar part of the evaluation of elevated liver enzymes, less common causes include autoimmune hepatitis, Wilson disease, and hereditary hemochromatosis. Each has a progressive course to end-organ damage underscoring the importance of early recognition, as effective therapies are available. Autoimmune hepatitis is an immune-mediated liver disease, with a female predominance and autoantibodies present in about 80% of cases. It can progress rapidly without treatment. Liver biopsy featuring lymphoplasmacytic hepatitis is needed for diagnosis and to determine the intensity of immunosuppression. Wilson disease is caused by biallelic variants in the ATP7B gene resulting in copper accumulation in the liver, brain, kidneys, and corneas. Diagnosis relies on clinical findings, laboratory data, and genetic testing results. Lifelong chelation therapy is required. Hereditary hemochromatosis is characterized by iron overload, usually due to a common variant in the HFE gene with variable disease penetrance; it is prevalent in people of Northern European ancestry. Untreated hemochromatosis leads to cirrhosis and hepatocellular carcinoma. Early diagnosis and initiation of phlebotomy can result in normal life expectancy. To facilitate early diagnosis, genetic testing of first-degree relatives is recommended for those with Wilson disease or hemochromatosis.
Male fertility concerns include prevention of pregnancy and planning for conception, including management of infertility. Male-directed contraception is currently limited to condom use or vasectomy. Vasectomy is a safe, office-based procedure that reliably results in sterility. Several options for reversible male contraception are currently under investigation. Use of high-dose testosterone with or without progestin and use of new androgens provide several potential pathways for reversible male contraception. Reversible occlusion of the vas deferens may provide a nonhormonal option for male contraception. Whereas some men seek contraception, other men experience infertility. Semen analysis is a key study to diagnose male infertility. Specific assisted reproduction technologies such as intrauterine insemination, in vitro fertilization, or intracytoplasmic sperm injection can prove useful in addressing male infertility. An important consideration for men who may be embarking on cancer treatment that could result in infertility is the use of sperm cryopreservation.
Alcohol-associated liver disease is the leading cause of cirrhosis in the United States and has become the top indication for liver transplantation since direct-acting antivirals allowed for cure of hepatitis C. The COVID-19 pandemic compounded existing concerns about a rising prevalence of alcohol-associated hepatitis, with a notable increase in women in their 30s and 40s. Insufficient access to health care continues to exacerbate socioeconomic disparities in screening and treatment. People identifying as American Indian or Alaska Native have had the greatest increase in mortality due to alcohol-associated liver disease. Alcohol use screening is essential for all adults. Abstinence from alcohol remains the cornerstone intervention for alcohol-associated liver disease, although pharmacotherapies are under evaluation. Noninvasive liver disease assessment, including serum and imaging modalities, is expanding access to advanced liver disease evaluation in primary care settings. Other causes of substance-based liver injury include prescription and nonprescription medications, herbal products, and dietary supplements.
Sodium disorders are commonly encountered in clinical practice and are frequently misunderstood. Abnormal serum sodium levels are due to an imbalance in free water. Hyponatremia and hypernatremia can be asymptomatic if mild and chronic; however, acute and severe changes in sodium levels may cause substantial symptoms. In acute mild hyponatremia, symptoms can include confusion, vomiting, and weakness. In severe cases, seizures can occur. Determining the patient's volume status helps to determine the underlying etiology and appropriate treatment strategy. Euvolemic hyponatremia is the most common presentation due to the prevalence of syndrome of inappropriate antidiuretic hormone. Depending on severity, hyponatremia can be managed in the outpatient or inpatient setting. Management is directed at treating underlying causes and relieving severe symptoms while decreasing the risk of serious adverse effects from treatment. In patients with chronic hyponatremia without severe symptoms, rapid correction of serum sodium should be avoided to minimize the risk of osmotic demyelination syndrome. Hypernatremia is caused by a loss of free water, inadequate water intake, or salt overload. Patients with acute hypernatremia may present with fatigue, signs of dehydration, and weakness. Symptomatic acute and severe hypernatremia require inpatient admission and management of free water deficit with intravenous hypotonic fluids.
A normal serum potassium level of 3.5 to 5.0 mEq/L is maintained via potassium ingestion, excretion, and distribution between intra- and extracellular fluid. Potassium balance is essential for maintenance of normal resting cell membrane potential in excitatory tissues. Abnormalities in serum potassium, whether low or high, can cause life-threatening complications due to cardiac, respiratory, or neurologic compromise. Hypokalemia results from renal or gastrointestinal losses, or transcellular shifts. In the absence of an identified cause, evaluation of urinary potassium excretion and acid-base status can help determine the etiology. Patients with severe (ie, serum potassium less than 2.5 mEq/L) or symptomatic hypokalemia should be admitted to the hospital for intravenous potassium replacement and cardiac monitoring. Patients with mild to moderate hypokalemia are often asymptomatic and can be treated with oral potassium while the underlying cause is addressed. Hyperkalemia is usually due to low urinary excretion, and less often to cellular release and transcellular shifts. Patients with acute hyperkalemia with associated electrocardiography findings and those with potassium levels 6.5 mEq/L or greater require inpatient treatment with calcium gluconate and other measures. Asymptomatic patients with chronic mild to moderate hyperkalemia can be managed as outpatients with dietary modification, diuretics, and medication adjustments.
Maintaining a normal physiologic acid-base balance is essential for the functioning of every organ system in the body. The renal and pulmonary systems are the primary regulators of acid-base balance. There are four principal acid-base disorders: metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. A systematic approach to evaluation is critical to identify potential etiologies. A history, physical examination, metabolic profile, and arterial blood gas measurement provide a full assessment of acid-base status. However, availability of arterial blood gas measurements is usually limited outside of inpatient and emergency department settings. Calculation of an anion gap is a crucial first step for evaluating laboratory test results. Changes in serum pH, Pco2, serum bicarbonate concentration, and anion gap suggest the primary disorder, and predictable compensatory changes indicate whether a secondary acid-base disturbance is present. Mixed acid-base disorders involving the renal and pulmonary systems can occur, underscoring the importance of a systematic approach to evaluation. In the outpatient setting, primary care physicians play a vital role in identifying and treating these disorders based on initial evaluation. Prompt recognition and management of acid-base disorders can help prevent morbidity and mortality.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a complex disease closely related to obesity and other cardiometabolic processes. It affects millions worldwide and is on track to markedly increase cases of end-stage liver disease requiring transplantation as well as cases of hepatocellular carcinoma in the coming years. Noninvasive assessments such as the Fibrosis-4 index are useful tools for identifying those at risk of clinically significant fibrosis and cirrhosis caused by MASLD. Other noninvasive tests, including liver stiffness measured with transient elastography, help to stratify risk, guide therapy, and inform surveillance and prognosis. Weight loss is the cornerstone of treatment for MASLD. The condition can progress to metabolic dysfunction-associated steatohepatitis (MASH), characterized by stage F2 or F3 fibrosis, and ultimately cirrhosis (stage F4 fibrosis). For patients with MASH who have comorbid obesity, bariatric surgery or pharmacologic approaches to weight loss should be considered. Progression to advanced fibrosis and cirrhosis (stage F3 or F4) is slow and depends on multiple factors. Screening for hepatocellular carcinoma with abdominal ultrasonography and alpha-fetoprotein testing every 6 months is indicated in patients with MASH-related cirrhosis.
More than 300 million people globally have viral hepatitis. Predominantly caused by hepatitis A, B, and C viruses, viral hepatitis continues to confer high levels of morbidity and mortality despite the availability of vaccines and advances in therapies. Symptom severity varies during acute infection, with management focused on stabilization and serial monitoring to ensure resolution of liver injury. Infection with hepatitis A virus is generally self-limited, with low but increasing rates of mortality and hospitalization due to factors such as poorer baseline health status, older age, and coexisting liver disease. About 95% of acute hepatitis B cases in adults resolve spontaneously; treatment is rarely needed in acute infection. In contrast, only about 25% of acute hepatitis C cases resolve spontaneously, and immediate initiation of treatment at diagnosis is recommended. Screening for hepatitis B and C is recommended for all adults. Hepatocellular carcinoma screening is recommended for those with hepatitis B and cirrhosis or specific risk factors, and for those with hepatitis C and advanced liver fibrosis or cirrhosis. Treatment of hepatitis B involves assessment of specific factors to determine antiviral need; the goal of treatment is suppression of viral replication, thereby reducing risks of liver disease progression and hepatocellular carcinoma. Curative medications are available for hepatitis C.
Maintaining a normal physiologic acid-base balance is essential for the functioning of every organ system in the body. The renal and pulmonary systems are the primary regulators of acid-base balance. There are four principal acid-base disorders: metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. A systematic approach to evaluation is critical to identify potential etiologies. A history, physical examination, metabolic profile, and arterial blood gas measurement provide a full assessment of acid-base status. However, availability of arterial blood gas measurements is usually limited outside of inpatient and emergency department settings. Calculation of an anion gap is a crucial first step for evaluating laboratory test results. Changes in serum pH, Pco2, serum bicarbonate concentration, and anion gap suggest the primary disorder, and predictable compensatory changes indicate whether a secondary acid-base disturbance is present. Mixed acid-base disorders involving the renal and pulmonary systems can occur, underscoring the importance of a systematic approach to evaluation. In the outpatient setting, primary care physicians play a vital role in identifying and treating these disorders based on initial evaluation. Prompt recognition and management of acid-base disorders can help prevent morbidity and mortality.
Melanoma is the fifth most common cancer in the United States and one of the deadliest. Tumor depth (Breslow depth) is the most important prognostic factor. Wide local excision is used to manage melanoma stage 0 (in situ) with 0.5- to 1-cm margins, as well as stage IA with 1-cm margins. For lentigo maligna (melanoma in situ), surgical margins wider than 0.5 cm are often necessary to achieve histologically negative margins, and comprehensive margin assessment techniques (Mohs surgery or staged excision) are associated with lower recurrence rates. Localized melanoma with a Breslow depth of less than 0.8 mm and without ulceration has an excellent prognosis and low risk for metastasis; standard treatment is wide local excision with 1-cm margins. Referral to subspecialists is required for melanoma stage IB or higher for discussion of sentinel lymph node biopsy and consideration of adjuvant therapies. Advances in sequencing have enabled tailored therapies for metastatic melanoma based on variations in somatic genes. Immunotherapy has improved survival in those with advanced melanoma. Genetic counseling should be considered for patients with a personal or family history of melanoma or certain other cancers (notably pancreatic cancer, uveal melanoma, mesothelioma, or astrocytoma). After a melanoma diagnosis, patients should undergo full skin examinations at least annually for surveillance..
Skin cancer is the most common cancer in the United States. Basal cell carcinoma, the leading type of skin cancer across all racial and ethnic groups, is usually slow growing and curable. Cutaneous squamous cell carcinoma accounts for more skin cancers in individuals with darker skin tones. Cutaneous melanoma is less common but potentially lethal in later stages. Patients with darker skin tones may have melanoma diagnosed at later stages, contributing to worse outcomes. Exposure to UV radiation is the primary risk factor for developing skin cancer. The US Preventive Services Task Force found insufficient evidence to recommend for or against routine visual skin cancer screening in asymptomatic adolescents and adults. Use of smartphone apps is not recommended because they are unreliable for detection. Artificial intelligence tools and teledermatology show promise for triage and access but are not yet standard for population-level skin cancer screening. Sun protection through public education, topical sunscreen application, UV protective clothing, and sun avoidance during peak UV hours remains the mainstay of skin cancer prevention. Oral nicotinamide reduces new nonmelanoma skin cancers in high-risk immunocompetent patients. Other chemopreventive agents, such as systemic retinoids, may be considered in select high-risk patients but are limited by adverse effects.
Actinic keratoses are precancerous skin lesions that are treated to prevent progression to cutaneous squamous cell carcinoma. Keratinocyte carcinomas include basal cell carcinoma and cutaneous squamous cell carcinoma. Cryosurgery is preferred to treat a single or limited number of actinic keratosis lesions, whereas field-directed therapies, such as topical fluorouracil, topical imiquimod, photodynamic therapy, topical tirbanibulin, and off-label topical fluorouracil plus calcipotriene, are preferred treatments for multiple lesions or significant field cancerization. For basal cell carcinoma, low-risk lesions may be treated with standard surgical excision, electrodesiccation and curettage, or topical agents for superficial subtypes. Basal cell carcinoma that is high risk or in cosmetically or functionally sensitive areas warrant Mohs surgery or similar techniques that provide complete margin assessment. Squamous cell carcinoma in situ can be managed with topical therapies, photodynamic therapy, electrodesiccation and curettage, or Mohs surgery for high-risk sites. Invasive cutaneous squamous cell carcinoma should be treated surgically, typically with 4- to 6-mm margins for low-risk tumors and Mohs surgery for tumors that are high-risk or located in cosmetically or functionally sensitive areas. Radiation is an alternative for patients who are not candidates for surgery. Systemic hedgehog pathway inhibitors are approved for locally advanced or metastatic basal cell carcinoma in patients who are not candidates for surgery or radiation therapy, although adverse effects often limit tolerance. Checkpoint inhibitor immunotherapy can be used in certain advanced cases of basal cell or cutaneous squamous cell carcinoma.
Family physicians play a critical role in early detection of skin cancers. Although visual inspection is the initial step, dermoscopy significantly improves diagnostic accuracy, particularly for melanoma and basal cell carcinoma. Advanced imaging technologies such as reflectance confocal microscopy, optical coherence tomography, and high-frequency ultrasonography may further enhance accuracy and reduce unnecessary procedures. However, these technologies are primarily used in academic or specialty dermatology settings. Biopsy is required for definitive diagnosis. For nonmelanoma skin cancers, no single biopsy technique has demonstrated superiority. A shave, punch, incisional, or excisional technique should be selected based on lesion characteristics, patient factors, and clinical judgment. For melanoma, excisional biopsy with margins of 1 to 3 mm and full-thickness removal is preferred. Saucerization (deep shave removal of the entire clinical lesion to the mid-dermis or deeper) may be acceptable if it allows accurate assessment of Breslow depth. Basal cell carcinoma subtypes include nodular, superficial, morpheaform (sclerosing), and infiltrative. Cutaneous squamous cell carcinoma is classified as in situ or invasive. The clinical subtypes of melanoma include superficial spreading, nodular, lentigo maligna melanoma, amelanotic, and acral lentiginous. If biopsy is not feasible because of lesion location or clinical suspicion persists despite benign histology, prompt dermatology referral is warranted.
